U.S. patent application number 14/508764 was filed with the patent office on 2015-01-22 for extracellular and membrane-associated prostate cancer markers.
This patent application is currently assigned to MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH. The applicant listed for this patent is Mayo Foundation for Medical Education and Research. Invention is credited to Eric W. Klee, George G. Klee, Farhad Kosari, George Vasmatzis.
Application Number | 20150024420 14/508764 |
Document ID | / |
Family ID | 39230524 |
Filed Date | 2015-01-22 |
United States Patent
Application |
20150024420 |
Kind Code |
A1 |
Klee; George G. ; et
al. |
January 22, 2015 |
EXTRACELLULAR AND MEMBRANE-ASSOCIATED PROSTATE CANCER MARKERS
Abstract
This document relates to methods and materials involved in
identifying, assessing, and monitoring prostate cancer in male
mammals. For example, this document provides arrays for detecting
polypeptides or nucleic acids that can be used to identify prostate
cancer in male mammals. In addition, methods and materials for
assessing and monitoring prostate cancer in mammals are provided
herein.
Inventors: |
Klee; George G.; (Rochester,
MN) ; Vasmatzis; George; (Oronoco, MN) ;
Kosari; Farhad; (Ellsworth, WI) ; Klee; Eric W.;
(Rochester, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Mayo Foundation for Medical Education and Research |
Rochester |
MN |
US |
|
|
Assignee: |
MAYO FOUNDATION FOR MEDICAL
EDUCATION AND RESEARCH
Rochester
MN
|
Family ID: |
39230524 |
Appl. No.: |
14/508764 |
Filed: |
October 7, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13607296 |
Sep 7, 2012 |
8871451 |
|
|
14508764 |
|
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|
12442685 |
Mar 24, 2009 |
8273539 |
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PCT/US2007/079423 |
Sep 25, 2007 |
|
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13607296 |
|
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60847057 |
Sep 25, 2006 |
|
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Current U.S.
Class: |
435/7.92 |
Current CPC
Class: |
C12Q 1/6886 20130101;
C12Q 2600/158 20130101; G01N 33/57488 20130101; G01N 2333/705
20130101; C12Q 2600/106 20130101; G01N 2333/96441 20130101; G01N
33/57434 20130101; G01N 2333/78 20130101; G01N 33/57492
20130101 |
Class at
Publication: |
435/7.92 |
International
Class: |
G01N 33/574 20060101
G01N033/574 |
Claims
1-5. (canceled)
6. A mass spectrometry method for identifying a male human as
having prostate cancer, said method comprising: (a) obtaining a
serum sample of a male human, (b) performing mass spectrometry to
detect the presence of an elevated level of a polypeptide encoded
by an ASPN, PCSK6, RPL22L1, or CDH7 nucleic acid within said
sample, and (c) classifying said male human as having prostate
cancer based at least in part on said presence.
7. The method of claim 6, wherein said polypeptide is a polypeptide
encoded by said ASPN nucleic acid.
8. The method of claim 6, wherein said polypeptide is a polypeptide
encoded by said PCSK6 nucleic acid.
9. The method of claim 6, wherein said polypeptide is a polypeptide
encoded by said RPL22L1 nucleic acid.
10. The method of claim 6, wherein said polypeptide is a
polypeptide encoded by said CDH7 nucleic acid.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 13/607,296, filed Sep. 7, 2012, which is a
continuation of U.S. patent application Ser. No. 12/442,685, filed
on Mar. 24, 2009 (now U.S. Pat. No. 8,273,539), which is a National
Stage application under 35 U.S.C. .sctn.371 of International
Application No. PCT/US2007/079423, having an International Filing
Date of Sep. 25, 2007, which claims the benefit of priority to U.S.
Provisional Patent Application Ser. No. 60/847,057, filed on Sep.
25, 2006. The disclosures of these applications are incorporated
herein by reference in their entirety.
BACKGROUND
[0002] 1. Technical Field
[0003] This document relates to methods and materials involved in
identifying, assessing, and monitoring prostate cancer in male
mammals.
[0004] 2. Background Information
[0005] Cancer is a general term for diseases characterized by
uncontrolled, abnormal growth of cells. The resulting mass, or
tumor, can invade and destroy surrounding normal tissues. In
addition, cancer cells from the tumor can spread through the blood
or lymph to start new cancers in other parts of the body, or
metastases.
[0006] Prostate cancer occurs when a malignant tumor forms in the
tissue of the prostate. The prostate is a gland in the male
reproductive system located below the bladder and in front of the
rectum. The main function of the prostate gland, which is about the
size of a walnut, is to make fluid for semen. Although there are
several cell types in the prostate, nearly all prostate cancers
start in the gland cells. This type of cancer is known as
adenocarcinoma.
[0007] Prostate cancer is the second leading cause of
cancer-related death in American men. Most of the time, prostate
cancer grows slowly. Autopsy studies show that many older men who
died of other diseases also had prostate cancer that neither they
nor their doctor were aware of Sometimes, however, prostate cancer
can grow and spread quickly. It is important to be able to
distinguish prostate cancers that will grow slowly from those that
will grow quickly since treatment can be especially effective when
the cancer has not spread beyond the region of the prostate.
Finding ways to detect cancers early can improve survival
rates.
SUMMARY
[0008] This document provides methods and materials related to
identifying, assessing, and monitoring prostate cancer in male
mammals (e.g., humans). For example, this document provides arrays
for detecting polypeptides or nucleic acids that can be used to
identify prostate cancer in mammals. Such arrays can allow prostate
cancer to be identified in mammals based on differences in the
levels of many polypeptides or nucleic acids in biological samples
from mammals that have prostate cancer as compared to the
corresponding levels in biological samples from mammals that do not
have prostate cancer.
[0009] Screening for prostate cancer has been widely performed by
measuring serum levels of prostate-specific antigen (PSA). However,
effective use of the PSA serum assay in general population
screening is inhibited by a lack of sensitivity and specificity.
Specific, sensitive, and non-invasive methods of screening mammals
for cancer (e.g., prostate cancer) can allow cancer to be detected
earlier. Early detection of cancer in mammals can allow the mammals
to be treated sooner and improve their prognosis. Screening methods
having adequate specificity with low false positive rates can
reduce unnecessary treatment and suffering.
[0010] This document is based, in part, on the discovery of nucleic
acid sequences that are predicted to encode extracellular or
membrane-associated polypeptides, and that are differentially
expressed in cancerous and non-cancerous prostate epithelial cells.
This document also is based, in part, on the discovery of nucleic
acid sequences that are predicted to encode polypeptides, and that
are expressed in prostate cells at a high level relative to other
cell types. The levels of transcripts and/or polypeptides encoded
by these nucleic acids can be used to distinguish mammals with
prostate cancer from mammals without prostate cancer. For example,
a mammal that is found to have serum containing one or more than
one polypeptide encoded by a nucleic acid listed in Table 2 at a
level that is different (e.g., greater than or less than) than the
average level observed in control serum can be classified as having
prostate cancer. In some cases, a mammal that is found to have
serum containing one or more than one polypeptide encoded by a
nucleic acid listed in Table 2 and one or more than one polypeptide
encoded by a nucleic acid listed in Table 3 at a level that is
different (e.g., greater than or less than) than the average level
observed in control serum can be classified as having prostate
cancer. In some cases, a mammal that is found to have prostate
cells expressing one or more than one polypeptide encoded by a
nucleic acid listed in Table 4 at a level that is greater than the
average level observed in control prostate cells can be classified
as having prostate cancer. The levels of nucleic acids and/or
polypeptides encoded by nucleic acids listed in Table 2 also can be
used to evaluate cancer aggressiveness, monitor cancer progression,
predict cancer outcome, and monitor response to treatment in
mammals. In some cases, the level of one or more than one nucleic
acid or polypeptide encoded by a nucleic acid listed in Table 2 and
the level of one or more than one nucleic acid or polypeptide
encoded by a nucleic acid listed in Table 3 can be used to evaluate
cancer aggressiveness, monitor cancer progression, predict cancer
outcome, or monitor the response to cancer treatment in
mammals.
[0011] In general, one aspect of this document features a method
for identifying a mammal as having prostate cancer. The method
comprising, or consists essentially of, (a) determining whether or
not a mammal has a prostate cancer fluid profile, and (b)
classifying the mammal as having prostate cancer if the mammal has
the prostate cancer fluid profile and classifying the mammal as not
having prostate cancer if the mammal does not have the prostate
cancer fluid profile. The mammal can be a human. The method can
comprise using blood, serum, plasma, urine, semen, or seminal fluid
to assess the presence or absence of the prostate cancer fluid
profile.
[0012] In another aspect, this document features a method for
identifying a mammal as having prostate cancer. The method
comprises, or consists essentially of, (a) determining whether or
not a mammal has a prostate cancer cell profile, and (b)
classifying the mammal as having prostate cancer if the mammal has
the prostate cancer cell profile and classifying the mammal as not
having prostate cancer if the mammal does not have the prostate
cancer cell profile. The mammal can be a human. The method can
comprise using prostate cells obtained from a needle biopsy to
assess the presence or absence of the prostate cancer cell
profile.
[0013] In another aspect, this document features a method for
assessing the effectiveness of a treatment for prostate cancer. The
method comprises, of consists essentially of, determining whether
or not a mammal having prostate cancer and having received a
treatment for the prostate cancer has a prostate cancer fluid
profile to the same or greater degree than that observed prior to
the treatment, wherein the presence of the prostate cancer fluid
profile to the same or greater degree than that observed prior to
the treatment indicates that the treatment is ineffective. The
mammal can be a human. The method can comprise using blood, serum,
plasma, urine, semen, or seminal fluid to assess the presence or
absence of the prostate cancer fluid profile to the same or greater
degree than that observed prior to the treatment.
[0014] In another aspect, this document features a method for
assessing the effectiveness of a treatment for prostate cancer. The
method comprises, or consists essentially of, determining whether
or not a mammal having prostate cancer and having received a
treatment for the prostate cancer has a prostate cancer cell
profile to the same or greater degree than that observed prior to
the treatment, wherein the presence of the prostate cancer cell
profile to the same or greater degree than that observed prior to
the treatment indicates that the treatment is ineffective. The
mammal can be a human. The method can comprise using prostate cells
obtained from a needle biopsy to assess the presence or absence of
the prostate cancer cell profile to the same or greater degree than
that observed prior to the treatment.
[0015] Unless otherwise defined, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention pertains.
Although methods and materials similar or equivalent to those
described herein can be used to practice the invention, suitable
methods and materials are described below. All publications, patent
applications, patents, and other references (e.g., the records
associated with GenBank accession or GI numbers) mentioned herein
are incorporated by reference in their entirety. In case of
conflict, the present specification, including definitions, will
control. In addition, the materials, methods, and examples are
illustrative only and not intended to be limiting.
[0016] The details of one or more embodiments of the invention are
set forth in the accompanying drawings and the description below.
Other features, objects, and advantages of the invention will be
apparent from the description and drawings, and from the
claims.
DETAILED DESCRIPTION
[0017] This document provides methods and materials related to
identifying, assessing, and monitoring prostate cancer in male
mammals. For example, this document provides arrays for detecting
nucleic acids or polypeptides that can be used to identify, assess,
and/or monitor prostate cancer in male mammals. Such arrays can
allow prostate cancer to be identified, assessed, and/or monitored
based on the levels of nucleic acids or polypeptides in a
biological sample from a mammal.
[0018] As described herein, this document provides methods and
materials for identifying prostate cancer in male mammals (e.g.,
humans). In some embodiments, a mammal can be classified as having
prostate cancer if it is determined that a biological fluid (e.g.,
blood, urine, seminal fluid, or serum) from the mammal contains one
or more than one polypeptide (e.g., two, three, four, five, six,
seven, eight, nine, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, or
more than 60 polypeptides), or a fragment thereof, encoded by a
nucleic acid listed in Table 2 (e.g., a category 1, 2, or 3 nucleic
acid listed in Table 2) at a level that is greater than the average
level of the same one or more than one polypeptide observed in
corresponding control fluid from control mammals. In some cases, a
mammal can be classified as having prostate cancer if it is
determined that a biological fluid (e.g., blood, urine, seminal
fluid, or serum) from the mammal contains one or more than one
polypeptide, or fragment thereof, encoded by a nucleic acid listed
in Table 2, and one or more than one polypeptide, or fragment
thereof, encoded by a nucleic acid listed in Table 3 at a level
that is greater than the average level of the same one or more than
one polypeptide observed in corresponding control fluid from
control mammals. In some cases, a mammal can be classified as
having prostate cancer if it is determined that prostate cells from
the mammal contain one or more than one nucleic acid or
polypeptide, or fragment thereof, encoded by a nucleic acid listed
in Table 4 (e.g., a category 1, 2, or 3 nucleic acid listed in
Table 4) at a level that is greater than the average level (e.g.,
via a subset analysis) of the same one or more than one nucleic
acid or polypeptide in corresponding control (e.g., non-cancerous)
prostate cells.
[0019] In some cases, a mammal can be classified as having prostate
cancer if it is determined that a biological fluid (e.g., blood,
urine, seminal fluid, or semen) from the mammal has a prostate
cancer fluid profile. For the purpose of this document, the term
"prostate cancer fluid profile" as used herein refers to a
polypeptide profile in a biological fluid (e.g., blood, plasma,
serum, urine, semen, or seminal fluid) where 16 or more (e.g., 18,
20, 25, 30, 35, 40, 45, 50, 55, 60, or more) polypeptides, or
fragments thereof, encoded by nucleic acids listed in Table 2 are
present at a level greater than the level observed in a
corresponding control biological fluid from a control mammal. In
some cases, the prostate cancer fluid profile can be a polypeptide
profile in a biological fluid where 25, 30, 35, 40, 45, 50, 55, 60,
65, 70, 75, 80, 85, 90, 95, or 100 percent of the polypeptides, or
fragments thereof, encoded by nucleic acids listed in Table 2 are
present at a level greater than the level observed in corresponding
control biological fluid from a control mammal.
[0020] In some cases, a mammal can be classified as having prostate
cancer if it is determined that prostate cells from the mammal have
a prostate cancer cell profile. The term "prostate cancer cell
profile" as used herein refers to a profile where prostate cells
express 12 or more (e.g., 15, 20, 25, 30, 35, 40, 45, 50, 55, 60,
or more) nucleic acids or polypeptides, or fragments thereof,
encoded by nucleic acids listed in Table 4 at a level greater than
the level observed in corresponding control prostate cells. In some
cases, the prostate cancer cell profile can be a profile in
prostate cells where 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75,
80, 85, 90, 95, or 100 percent of the nucleic acids or
polypeptides, or fragments thereof, encoded by nucleic acids listed
in Table 4 are present at a level greater than the level observed
in corresponding control prostate cells.
[0021] Prostate cancer can be identified in any male mammal such as
a male human, dog, horse, mouse, or rat. The mammal can be
middle-aged or older. For example, a male human can be 35 years old
or older (e.g., 40, 45, 50, 55, 60, 65, 70, 75 years old or
older).
[0022] Any biological fluid can be evaluated to determine if it
contains one or more than one polypeptide or nucleic acid, or
fragment thereof, encoded by a nucleic acid listed in Table 2 at a
level that is greater than the average level observed in a
corresponding control biological fluid. For example, blood (e.g.,
peripheral blood or venous prostate blood), plasma, serum, urine,
semen, and/or seminal fluid can be evaluated to determine if the
fluid contains one or more than one polypeptide or nucleic acid
encoded by a nucleic acid listed in Table 2 at a level that is
greater than the average level observed in a corresponding control
biological fluid. In some cases, a biological fluid (e.g., blood,
plasma, serum, urine, semen, and/or seminal fluid) can be evaluated
to determine if the fluid contains one or more than one polypeptide
or nucleic acid, or fragment thereof, encoded by a nucleic acid
listed in Table 2, and one or more than one polypeptide or nucleic
acid, or fragment thereof, encoded by a nucleic acid listed in
Table 3 at a level that is greater than the average level observed
in a corresponding control biological fluid. In some cases, a
biological fluid can be evaluated to determine if the fluid has a
prostate cancer fluid profile.
[0023] Any type of biological sample can be evaluated to determine
if it contains one or more than one nucleic acid or polypeptide, or
fragment thereof, encoded by a nucleic acid listed in Table 4 at a
level that is greater than the average level observed in a
corresponding control biological sample. For example, biological
fluids can be evaluated including, without limitation, blood,
plasma, serum, urine, semen, and seminal fluid. In some cases,
prostate cells can be evaluated including, without limitation,
prostate cells in prostate tissue and metastatic prostate cancer
cells in blood, urine, cellular fragments, or in tissues other than
prostate tissue such as lung tissue and lymph node tissue. In some
cases, prostate cells can be evaluated to determine whether or not
the cells have a prostate cancer cell profile.
[0024] Any method can be used to obtain a biological sample from a
mammal. For example, a blood sample can be obtained by peripheral
venipuncture, and urine samples can be obtained using standard
urine collection techniques. In some cases, a tissue sample can be
obtained from a tissue biopsy (e.g., a needle biopsy), from a
transurethral resection of the prostate (TURP), or from a radical
prostatectomy. A sample can be manipulated prior to being evaluated
for the level of one or more than one nucleic acid or polypeptide
encoded by a nucleic acid listed in Table 2 or 3. A sample also can
be manipulated prior to being evaluated for a prostate cancer fluid
profile or a prostate cancer cell profile. For example, a prostate
biopsy specimen can be frozen, embedded, and/or sectioned prior to
being evaluated. In addition, nucleic acids and/or polypeptides can
be extracted from a sample, purified, and evaluated to determine
the level of one or more than one nucleic acid or polypeptide
encoded by a nucleic acid listed in Table 2 or 3. In some cases,
nucleic acids and/or polypeptides extracted from a sample can be
evaluated for a prostate cancer cell profile or a prostate cancer
fluid profile. In some cases, a tissue sample can be disrupted to
obtain a cell lysate. Once obtained, the cell lysate can be
analyzed for the level of one or more than one polypeptide encoded
by a nucleic acid listed in Table 4. A cell lysate also can be
evaluated for a prostate cancer cell profile. In some cases,
prostate cells can be isolated from other cells or tissues prior to
analysis. For example, prostate cells can be isolated from tissues
using laser capture microdissection prior to being evaluated for
the level of one or more than one nucleic acid or polypeptide
encoded by a nucleic acid listed in Table 4. In some cases,
prostate cells can be evaluated for a prostate cancer cell
profile.
[0025] The level of any number of nucleic acids or polypeptides
encoded by nucleic acids listed in Table 2 can be evaluated to
identify prostate cancer. For example, the level of one or more
than one (e.g., two, three, four, five, six, seven, eight, nine,
10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, or more than 60)
nucleic acid or polypeptide encoded by a nucleic acid listed in
Table 2 can be used to identify prostate cancer. In some cases, the
level of one or more than one (e.g., two, three, four, five, six,
seven, eight, nine, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, or
more than 60) nucleic acid or polypeptide encoded by a nucleic acid
listed in Table 2, and the level of one or more than one (e.g.,
two, three, four, five, six, or more than 6) nucleic acid or
polypeptide encoded by a nucleic acid listed in Table 3 can be used
to identify prostate cancer. In some cases, the level of one or
more than one (e.g., two, three, four, five, six, seven, eight,
nine, 10, 15, 20, 25, 30, 35, 40, 45, 50, or more than 50) nucleic
acid or polypeptide encoded by a nucleic acid listed in Table 4 can
be used to identify prostate cancer.
[0026] The level of a nucleic acid or polypeptide encoded by a
nucleic acid listed in Table 2 or 3 in a biological sample can be
greater than or less than the average level observed in
corresponding control samples. Typically, a nucleic acid or
polypeptide can be classified as being present at a level that is
greater than or less than the average level observed in control
samples if the levels differ by at least 10, 20, 30, 40, 50, 60,
70, 80, 90, or more percent. In some cases, a nucleic acid or
polypeptide can be classified as being present at a level that is
greater than or less than the average level observed in control
samples if the levels differ by greater than 1-fold (e.g.,
1.5-fold, 2-fold, 3-fold, or more than 3-fold). Control samples
typically are obtained from one or more mammals of the same species
as the mammal being evaluated. When identifying prostate cancer,
control samples (e.g., control serum or urine samples) can be
obtained from healthy mammals, such as male humans who do not have
prostate cancer. In some cases, control samples can be
non-cancerous prostate cells or tissues from male mammals having
prostate cancer (e.g., non-neoplastic cells adjacent to prostate
cancer cells). Control samples can be obtained from any number of
mammals. For example, control samples can be obtained from one or
more mammals (e.g., 10, 20, 30, 40, 50, 75, 100, 200, 300, 400,
500, 1000, or more than 1000 mammals) from the same species as the
mammal being evaluated.
[0027] Any method can be used to determine whether or not a
polypeptide is present in a biological sample at a level that is
greater than or less than the average level observed in
corresponding control samples. For example, the level of a
particular polypeptide can be measured using, without limitation,
immuno-based assays (e.g., ELISA and immunohistochemistry), Western
blotting, arrays for detecting polypeptides, two-dimensional gel
analysis, chromatographic separation, mass spectrometry (MS),
tandem mass spectrometry (MS/MS), or liquid chromatography (LC)-MS.
Methods of using arrays for detecting polypeptides include, without
limitation, those described herein. Such methods can be used to
determine simultaneously the relative levels of multiple
polypeptides.
[0028] Any method can be used to determine whether or not a
specific nucleic acid is present in a biological samples at a level
that is greater than or less than the average level observed in
corresponding control samples. For example, the level of a
particular nucleic acid can be measured using, without limitation,
Northern blotting, slot blotting, quantitative PCR, RT-PCR, or chip
hybridization techniques. Methods for chip hybridization assays
include, without limitation, those described herein. Such methods
can be used to determine simultaneously the relative expression
levels of multiple nucleic acids.
[0029] Methods provided herein for identifying prostate cancer in
male mammals can be used in combination with one or more methods
typically used to identify prostate cancer. Such methods include,
without limitation, digital rectal exam, transrectal
ultrasonography, intravenous pyelogram, cystoscopy, and blood and
urine tests for levels of prostatic acid phosphatase (PAP) and PSA.
A mammal can be evaluated regularly for prostate cancer. For
example, a mammal can be evaluated once a year for as long as the
mammal is alive. In some cases, male humans can be evaluated for
prostate cancer once every year beginning at age 35. Mammals that
are susceptible to develop prostate cancer can be screened more
frequently, and screening can be started at an earlier age. For
example, mammals having a genetic predisposition to develop cancer,
a family history of cancer, or a trend towards an increased serum
level of one or more polypeptides encoded by a nucleic acid listed
in Table 2 can be assessed more frequently.
[0030] This document also provides materials and methods for
assessing prostate cancer in a mammal. For example, this document
provides materials and methods for assessing the aggressiveness of
prostate cancer in a mammal. Methods typically used to assess the
aggressiveness of prostate cancer in a mammal include determining
the Gleason score, the serum PSA level, and whether or not the
serum PSA level increases over time and rate of PSA increases (PSA
velocity). The Gleason score is a measure of how different cancer
cells are from normal cells. The more different the cancer cells
are from non-cancer cells, the more likely that the cancer will
spread quickly. In some cases, the aggressiveness of prostate
cancer can be assessed based on the numbers and/or levels of
nucleic acids or polypeptides encoded by nucleic acids listed in
Table 2 in a biological fluid from a mammal. The greater the number
of different nucleic acids or polypeptides encoded by nucleic acids
listed in Table 2 in a biological fluid from the mammal, the more
aggressive the prostate cancer in the mammal. In addition, the
greater the differences between the levels of the nucleic acids or
polypeptides encoded by nucleic acids listed in Table 2 in a
biological fluid from a mammal and the average levels of the same
nucleic acids or polypeptides in control samples, the more likely
the prostate cancer will move rapidly and progress in the mammal.
In some embodiments, the aggressiveness of prostate cancer can be
assessed based on the levels of nucleic acids or polypeptides
encoded by nucleic acids listed in Table 2, and the level of one or
more than one nucleic acid or polypeptide encoded by a nucleic acid
listed in Table 3 in a biological fluid from a mammal. In some
cases, the levels of nucleic acids or polypeptides encoded by
nucleic acids listed in Table 2 in a biological fluid can be used
in combination with one or more other factors to determine whether
or not a mammal having prostate cancer is susceptible to a poor
outcome. For example, levels of nucleic acids or polypeptides
encoded by nucleic acids listed in Table 2 in a biological fluid
from a mammal having prostate cancer can be used in combination
with the clinical stage, the serum PSA level, and/or the Gleason
pattern of the prostate cancer to determine whether or not the
mammal is likely to have to a poor outcome. In some cases, the
aggressiveness of prostate cancer can be assessed based on the
numbers and/or levels of nucleic acids or polypeptides encoded by
nucleic acids listed in Table 4 in a biological sample from a
mammal.
[0031] Information about the aggressiveness of prostate cancer can
be used to guide treatment selection. For example, a mammal
identified as having more aggressive prostate cancer can be treated
earlier and more aggressively than a mammal identified as having
less aggressive prostate cancer. A more aggressive treatment can
include radical prostatectomy. A mammal identified as having less
aggressive prostate cancer may undergo "watchful waiting" while
having little or no standard treatment, particularly if the mammal
is elderly.
[0032] Once prostate cancer has been identified in a mammal (e.g.,
a human), the mammal can be subsequently evaluated or monitored
over time for progression of the cancer, particularly if the cancer
was identified as being aggressive. For example, prostate cancer in
a mammal can be assessed as having progressed if it is determined
that a biological fluid from the mammal (e.g., serum or urine from
the mammal) contains one or more than one nucleic acid or
polypeptide encoded by a nucleic acid listed in Table 2 at a level
that is greater than the level of the same one or more than one
nucleic acid or polypeptide observed in a corresponding biological
fluid (e.g., serum or urine) obtained previously from the same
mammal. In some cases, prostate cancer in a mammal can be assessed
as having progressed if it is determined that a biological fluid
from the mammal (e.g., serum or urine from the mammal) contains one
or more than one nucleic acid or polypeptide encoded by a nucleic
acid listed in Table 2, and one or more than one nucleic acid or
polypeptide encoded by a nucleic acid listed in Table 3 at a level
that is greater than the level of the same one or more nucleic
acids or polypeptides observed in a corresponding biological fluid
(e.g., serum or urine) obtained previously from the same mammal. In
some cases, prostate cancer in a mammal can be assessed as having
progressed if it is determined that a biological fluid from the
mammal has a prostate cancer fluid profile to a level greater than
that observed in a corresponding biological fluid obtained
previously from the same mammal. In some cases, prostate cancer in
a mammal can be assessed as having progressed if it is determined
that a sample (e.g., a sample of prostate cells) from the mammal
contains one or more than one nucleic acid or polypeptide encoded
by a nucleic acid listed in Table 4 at a level that is greater than
the level of the same one or more than nucleic acid or polypeptide
observed in a corresponding sample obtained previously from the
same mammal. In some cases, prostate cancer in a mammal can be
assessed as having progressed if it is determined that a sample
(e.g., a sample of prostate cells) from the mammal has a prostate
cancer cell profile to a level greater than that observed in a
corresponding sample obtained previously from the same mammal. A
mammal can be monitored for progression of prostate cancer over any
period of time with any frequency. For example, a male mammal can
be monitored once a year, twice a year, three times a year, or more
frequently. In some cases, a mammal can be monitored every three
months for five years or once a year for as long as the mammal is
alive.
[0033] A mammal can also be assessed for progression of prostate
cancer before, during, and after treatment for prostate cancer. For
example, a mammal can be assessed for progression (e.g.,
metastasis) of prostate cancer while being treated with androgen
deprivation therapy or following radical prostatectomy. Assessing a
mammal for progression of prostate cancer during treatment of the
mammal for prostate cancer can allow the effectiveness of the
prostate cancer therapy to be determined. For example, a decrease
in the level of one or more than one nucleic acid or polypeptide
encoded by a nucleic acid listed in Table 2 in a biological fluid
(e.g., serum or urine) from a mammal being treated for prostate
cancer as compared to the level of the same one or more nucleic
acids or polypeptides observed in a corresponding biological fluid
(e.g., serum or urine) obtained previously from the same mammal can
indicate that the therapy is effective. In some cases, a therapy
can be assessed as being effective if it is determined that a fluid
from a mammal having prostate cancer and having received a prostate
cancer treatment has a prostate cancer fluid profile to a level
less than that observed in corresponding fluid from the same mammal
prior to the treatment.
[0034] This document also provides methods and materials to assist
medical or research professionals in determining whether or not a
mammal has prostate cancer. Medical professionals can be, for
example, doctors, nurses, medical laboratory technologists, and
pharmacists. Research professionals can be, for example, principle
investigators, research technicians, postdoctoral trainees, and
graduate students. A professional can be assisted by (1)
determining the level of one or more than one polypeptide or
nucleic acid encoded by a nucleic acid listed in Table 2 in a
sample, and (2) communicating information about that level to that
professional.
[0035] Any method can be used to communicate information to another
person (e.g., a professional). For example, information can be
given directly or indirectly to a professional. In addition, any
type of communication can be used to communicate the information.
For example, mail, e-mail, telephone, and face-to-face interactions
can be used. The information also can be communicated to a
professional by making that information electronically available to
the professional. For example, the information can be communicated
to a professional by placing the information on a computer database
such that the professional can access the information. In addition,
the information can be communicated to a hospital, clinic, or
research facility serving as an agent for the professional.
[0036] This document also provides arrays for detecting
polypeptides. The arrays provided herein can be two-dimensional
arrays, and can contain at least two different polypeptides capable
of detecting polypeptides, such as antibodies (e.g., at least
three, at least five, at least ten, at least 20, at least 30, at
least 40, at least 50, or at least 60 different polypeptides
capable of detecting polypeptides). The arrays provided herein also
can contain multiple copies of each of many different polypeptides.
In addition, the arrays for detecting polypeptides provided herein
can contain polypeptides attached to any suitable surface (e.g.,
plastic or glass).
[0037] A polypeptide capable of detecting a polypeptide can be
naturally occurring, recombinant, or synthetic. The polypeptides
immobilized on an array also can be antibodies. An antibody can be,
without limitation, a polyclonal, monoclonal, human, humanized,
chimeric, or single-chain antibody, or an antibody fragment having
binding activity, such as a Fab fragment, F(ab') fragment, Fd
fragment, fragment produced by a Fab expression library, fragment
comprising a VL or VH domain, or epitope binding fragment of any of
the above. An antibody can be of any type, (e.g., IgG, IgM, IgD,
IgA or IgY), class (e.g., IgG1, IgG4, or IgA2), or subclass. In
addition, an antibody can be from any animal including birds and
mammals. For example, an antibody can be a mouse, chicken, human,
rabbit, sheep, or goat antibody. Such an antibody can be capable of
binding specifically to a polypeptide encoded by a nucleic acid
listed in Table 2 or 3. The polypeptides immobilized on the array
can be members of a family such as a receptor family, protease
family, or an enzyme family.
[0038] Antibodies can be generated and purified using any suitable
methods known in the art. For example, monoclonal antibodies can be
prepared using hybridoma, recombinant, or phage display technology,
or a combination of such techniques. In some cases, antibody
fragments can be produced synthetically or recombinantly from a
nucleic acid encoding the partial antibody sequence. In some cases,
an antibody fragment can be enzymatically or chemically produced by
fragmentation of an intact antibody. In addition, numerous
antibodies are available commercially (Table 1). An antibody
directed against a polypeptide encoded by a nucleic acid listed in
Table 2 or 3 can bind the polypeptide at an affinity of at least
10.sup.4 mol.sup.-1 (e.g., at least 10.sup.5, 10.sup.6, 10.sup.7,
10.sup.8, 10.sup.9, 10.sup.10, 10.sup.11, or 10.sup.12
mol.sup.-1).
TABLE-US-00001 TABLE 1 Commercially available antibodies directed
against extracellular or membrane-associated polypeptides Nucleic
Acid Symbol Antibody Name Supplier Catalog No. Clone APOC1
Apolipoprotein C-1 Abcam, ab20120 mouse antibody Cambridge, MA ASPN
Asporin antibody Imgenex, San IMG-3803 goat Diego, CA C20orf102
C20orf102 antibody Abnova, Taipei, H00128434- clone 3B9 Taiwan M01
COL2A1 COL2A1 monoclonal Abnova, Taipei, H00001280- #3H1-9 antibody
Taiwan M01 HLA-DMB HLA-DMB monoclonal Abnova, Taipei, H00003109-
clone 6B3 antibody Taiwan M01 MMP26 Rabbit antibody to Triple Point
RP3MMP26 rabbit MMP-26 Biologics, Forest Grove, OR NRN1 Anti-human
Neuritin R&D Systems, AF283 goat antibody Minneapolis, MN SFRP4
SFRP4 polyclonal Abnova, Taipei, H00006424- mouse poly antibody
Taiwan A01 CHRM3 CHRM3 polyclonal Abnova, Taipei, H00001131- mouse
poly antibody Taiwan A01 OR51E2 PSGR antibody Novus, Littleton,
ab13383 rabbit CO TMPRSS2 TMPRSS2 (h-50) Santa Cruz sc-33533 rabbit
antibody Biotechnology, Santa Cruz, CA PLA2G7 PLA2G7 monoclonal
Abnova, Taipei, H00007941- clone 5D1 antibody Taiwan M02 FZD8 FZD8
polycolonal Abnova, Taipei, H00008325- mouse poly antibody Taiwan
A01 GJB1 Connexin 32/GJB1 Abcam, ab11366 CXN-32 antibody [CXN-32]
Cambridge, MA MSMB Prostate Secretory Abcam, ab19070 YPSP-1
Protein/PSP antibody Cambridge, MA [YPSP-1] MSMB MSMB polyclonal
Abnova, Taipei, H00004477- mouse poly antibody Taiwan A01 MSMB Mab
to human Prostate BIODESIGN, M14841M BDI841 Secretory protein Saco,
ME MSMB Mab to human Prostate BIODESIGN, M14248M BDI248 Secretory
protein Saco, ME MSMB MSMB polyclonal Novus, Littleton, H00004477-
mouse poly antibody CO A01 ADAMTS8 ADAMTS8 antibody Abcam, ab28597
rabbit Cambridge, MA ADAMTS8 ADAMTS8 monoclonal Abnova, Taipei,
H00011095- clone 5A3 antibody Taiwan M01 ADAMTS8 Rabbit anti ADAM-
Accurate, ACL2ADA rabbit TS8, amino terminal Westbury, NY MTS8
ADAMTS8 Rabbit anti ADAM- Accurate, ACL1ADA rabbit TS8, carboxy
terminal Westbury, NY MTS8 ALDH3B2 ALDH3B2 monoclonal Abnova,
Taipei, H00000222- clone 3E6 antibody Taiwan M01 EFNA4 Ephrin A4
Antibody Novus, Littleton, ab7041 goat CO GRIN3A NMDAR3A + 3B
Abcam, ab2639 mouse Cambridge, MA GRIN3A NMDAR3A + 3B Novus,
Littleton, H00002904- mouse antibody CO A01 GRIN3A NMDAR NR3A/B
QED, San Diego, 60100 rabbit antibody CA HPN Hepsin antibody Abcam
, ab31149 Duck/IgY Cambridge, MA HPN Hepsin antibody Abcam, ab31148
rabbit Cambridge, MA HPN HPN monoclonal Abnova, Taipei, H00003249-
clone 3E3 antibody Taiwan M01 ITGBL1 Osteoblast Specific Abcam,
ab37176 chicken/IgY Cysteine-rich Protein Cambridge, MA LOX LOX
antibody Abcam , ab31238 rabbit Cambridge, MA MUC1 MUC-1 polyclonal
Abnova, Taipei, H00004582- mouse poly antibody Taiwan A01 NRP1 NRP1
monoclonal Abnova, Taipei, H00008829- 1B3 antibody Taiwan M05 NRP1
Anti-Neuropilin-1 (CUB ECM Biosciences NP2111 rabbit Domain) NRP1
Neuropilin (A-12) Santa Cruz sc-5307 mouse mono antibody
Biotechnology, Santa Cruz, CA PCDHB10 PCDHB10 polyclonal Abnova,
Taipei, H00056126- mouse poly antibody Taiwan A01 PCSK6 PCSK6
plyclonal Abnova, Taipei, H00005046- mouse poly antibody Taiwan A01
PSCA PSCA monoclonal Abnova, Taipei, H00008000- 5c2 antibody Taiwan
M03
[0039] Any method can be used to make an array for detecting
polypeptides. For example, methods disclosed in U.S. Pat. No.
6,630,358 can be used to make arrays for detecting polypeptides.
Arrays for detecting polypeptides can also be obtained
commercially, such as from Panomics, Redwood City, Calif.
[0040] This document also provides nucleic acid arrays. The arrays
provided herein can be two-dimensional arrays, and can contain at
least two different nucleic acid molecules (e.g., at least three,
at least five, at least ten, at least 20, at least 30, at least 40,
at least 50, or at least 60 different nucleic acid molecules). Each
nucleic acid molecule can have any length. For example, each
nucleic acid molecule can be between 10 and 250 nucleotides (e.g.,
between 12 and 200, 14 and 175, 15 and 150, 16 and 125, 18 and 100,
20 and 75, or 25 and 50 nucleotides) in length. In some cases, an
array can contain one or more cDNA molecules encoding, for example,
partial or entire polypeptides. In addition, each nucleic acid
molecule can have any sequence. For example, the nucleic acid
molecules of the arrays provided herein can contain sequences that
are present within the nucleic acids listed in Tables 2 and 3.
[0041] Typically, at least 25% (e.g., at least 30%, at least 40%,
at least 50%, at least 60%, at least 75%, at least 80%, at least
90%, at least 95%, or 100%) of the nucleic acid molecules of an
array provided herein contain a sequence that is (1) at least 10
nucleotides (e.g., at least 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
25, or more nucleotides) in length and (2) at least about 95
percent (e.g., at least about 96, 97, 98, 99, or 100) percent
identical, over that length, to a sequence present within a nucleic
acid listed in Table 2 or 3. For example, an array can contain 60
nucleic acid molecules located in known positions, where each of
the 60 nucleic acid molecules is 100 nucleotides in length while
containing a sequence that is (1) 30 nucleotides is length, and (2)
100 percent identical, over that 30 nucleotide length, to a
sequence of one of the nucleic acids listed in Table 2. Thus, a
nucleic acid molecule of an array provided herein can contain a
sequence present within a nucleic acid listed in Table 2 or 3 where
that sequence contains one or more (e.g., one, two, three, four, or
more) mismatches.
[0042] The nucleic acid arrays provided herein can contain nucleic
acid molecules attached to any suitable surface (e.g., plastic or
glass). In addition, any method can be use to make a nucleic acid
array. For example, spotting techniques and in situ synthesis
techniques can be used to make nucleic acid arrays. Further, the
methods disclosed in U.S. Pat. Nos. 5,744,305 and 5,143,854 can be
used to make nucleic acid arrays.
[0043] In some cases, a sample from a mammal can be assessed for
auto-antibodies against a polypeptide encoded by any of the nucleic
acid molecules provided herein. The presence of such
auto-antibodies can indicate that the mammal has prostate cancer.
For example, a blood sample from a human can be assessed for the
presence of auto-antibodies to a polypeptide encoded by any of the
nucleic acid molecules provided herein with the presence of such an
auto-antibody indicating that that human has prostate cancer.
[0044] The invention will be further described in the following
examples, which do not limit the scope of the invention described
in the claims.
EXAMPLES
Example 1
Identification of Nucleic Acids Encoding Extracellular and
Membrane-Associated Polypeptides that can be Used to Identify
Prostate Cancer
[0045] Gene expression was profiled in prostate epithelial cells.
Benign and malignant cells were laser capture microdissected from
100 prostate tissues and metastatic prostatic adenocarcinomas.
Non-neoplastic prostate epithelial cells were collected from the
tissues of 29 patients having prostate cancer. High-grade prostatic
intraepithelial neoplasia (PIN) cells, metastatic prostate cancer
cells, and primary Gleason pattern 3, 4, and 5 cells were collected
from the remaining tissues. RNA was extracted from homogenous
populations of captured cells and purified. Samples of total RNA
were linearly amplified, labeled, and hybridized to U133 Plus 2.0
arrays (Affymetrix, Santa Clara, Calif.). The arrays were washed,
stained, and scanned in accordance with Affymetrix protocols.
[0046] Secreted and membrane bound polypeptides associated with the
Affymetrix probe sets were identified using two methods. First,
RefSeq polypeptide sequence identifiers annotated to the probe set
identifiers were abstracted from the Affymetrix U133 Plus 2.0
annotation file. These sequences were downloaded from NCBI and
processed through a prediction pipeline, which included SignalP
analysis, TargetP analysis, TMHMM analysis, and Phobius analysis.
Polypeptides predicted to be secretory polypeptides by the SignalP
and TargetP programs were further analyzed using the TMHMM and
Phobius programs. Polypeptides that were not predicted to be
secretory polypeptides by the SignalP program or the TargetP
program were classified as non-secretory polypeptides. Secretory
polypeptides predicted to have no transmembrane domains by the
TMHMM program were classified as extracellular. Secretory
polypeptides predicted to have two or more transmembrane domains
were classified as membrane-associated polypeptides. Secretory
polypeptides predicted to have only one transmembrane domain were
analyzed using the Phobius program. Phobius predictions were used
to differentiate polypeptides with N-terminal signal anchors
(uncleaved) from polypeptides with N-terminal signal sequences
(cleaved). The second method used to identify secreted and membrane
polypeptides involved mining the localization annotated database of
SWISS-PROT polypeptides. The SwissProt records for all human
polypeptides were downloaded. All localization annotations were
manually reviewed and categorized as extracellular (S), plasma
membrane (M), or intracellular (I). All probe sets with annotated
SwissProt polypeptides having cellular localization annotations
were classified extracellular (S), plasma membrane (M), or
intracellular (I). Localization classifications assigned by
SwissProt annotations were given preference over classifications
made by the prediction analyses. A set of 70 nucleic acids encoding
extracellular and membrane-associated polypeptides was identified,
including 53 nucleic acids that were annotated or predicted to
encode extracellular polypeptides, and 17 nucleic acids that were
annotated or predicted to encode membrane-associated
polypeptides.
[0047] The value of the selected nucleic acids for use in
identifying cancer was assessed using two methods. Fifty-four
polypeptides, including all of the membrane-associated
polypeptides, were selected based on up-regulation of corresponding
RNA transcripts observed in prostate cancer cells as compared to
non-neoplastic prostate cells. The initial list of differentially
expressed nucleic acids was identified using several microarray
analysis parameters, including:
[0048] a. PM/MM normalization and no transformation
[0049] b. PM only normalization and no transformation
[0050] c. PM/MM normalization and log2 transformation
[0051] d. PM only normalization and log2 transformation
[0052] Expression values generated from these analysis methods were
then used to make the following comparisons:
[0053] a. Gleason pattern 3 versus [0054] Non-neoplastic (excluding
Benign Prostatic Hyperplasia (BPH))
[0055] b. Gleason pattern 3 versus [0056] Non-neoplastic+BPH
[0057] c. Gleason pattern 3+Gleason pattern 4 versus [0058]
Non-neoplastic (excluding BPH)
[0059] d. Gleason pattern 3+Gleason pattern 4 versus [0060]
Non-neoplastic+BPH
[0061] e. All Cancer versus [0062] Non-neoplastic (excluding
BPH)
[0063] f. All Cancer versus [0064] Non-neoplastic+BPH
[0065] Nucleic acids demonstrating at least two fold up-regulation
in cancer cells compared to non-neoplastic cells were
cross-referenced with nucleic acids classified as encoding either
secretory or membrane-associated polypeptides. The resulting list
of nucleic acids was manually curated to remove cases with
expression levels below the noise level of the microarray
experiment, and cases having an expression profile that was
over-biased by one or two aberrant cases.
[0066] The remaining sixteen nucleic acids were selected because
they had a high level of expression in prostate cells and a
prostate-preferential expression profile, without clear
differential expression between cancer and non-cancer cells. Tissue
specificity was quantitated by mining Expressed Sequence Tag
transcripts.
[0067] The 70 nucleic acids selected were cross-referenced with the
Cancer Genome Anatomy Project's SAGE Genie, the Ludwig Institute
for Cancer Research MPSS database, the Human Protein Atlas
database, and an EST tissue specificity analysis database. Based on
these additional transcriptomic and immunohistochemistry
annotations, the nucleic acids were prioritized with numeric
rankings from 1 (highest priority) to three (lowest priority). The
selected nucleic acids are listed in Tables 2-4.
TABLE-US-00002 TABLE 2 Nucleic acids encoding extracellular or
membrane-associated polypeptides that can be used to identify
prostate cancer. Nucleic RefSeq Acid Protein Local- Symbol
Selection Process Identifier Category ization APOC1 Increased
expression NP_001636.1 1 Extra- in cancer cells versus cellular
non-cancer cells ASPN Increased expression NP_060150.3 1 Extra- in
cancer cells versus cellular non-cancer cells BCMP11 Increased
expression NP_789783.1 1 Extra- in cancer cells versus cellular
non-cancer cells C20orf102 Increased expression NP_542174.1 1
Extra- in cancer cells versus cellular non-cancer cells COL2A1
Increased expression NP_001835.2 1 Extra- in cancer cells versus
NP_149162.1 cellular non-cancer cells F5 Increased expression
NP_000121.1 1 Extra- in cancer cells versus cellular non-cancer
cells HLA-DMB Increased expression NP_002109.1 1 Extra- in cancer
cells versus cellular non-cancer cells LRRN1 Increased expression
NP_065924.2 1 Extra- in cancer cells versus cellular non-cancer
cells MMP26 Increased expression NP_068573.2 1 Extra- in cancer
cells versus cellular non-cancer cells NRN1 Increased expression
NP_057672.1 1 Extra- in cancer cells versus cellular non-cancer
cells OGDHL Increased expression NP_060715.1 1 Extra- in cancer
cells versus cellular non-cancer cells PLA1A Increased expression
NP_056984.1 1 Extra- in cancer cells versus cellular non-cancer
cells PLA2G7 Increased expression NP_005075.2 1 Extra- in cancer
cells versus cellular non-cancer cells SFRP4 Increased expression
NP_003005.1 1 Extra- in cancer cells versus cellular non-cancer
cells ALDH3B2 Increased expression NP_000686.2 2 Extra- in cancer
cells versus NP_ cellular non-cancer cells 001026786.1 APOF
Increased expression NP_001629.1 2 Extra- in cancer cells versus
cellular non-cancer cells B3Gn-T6 Increased expression NP_619651.2
2 Extra- in cancer cells versus cellular non-cancer cells C4A///C4B
Increased expression NP_ 2 Extra- in cancer cells versus
001002029.1 cellular non-cancer cells NP_009224.2 COL9A2 Increased
expression NP_001843.1 2 Extra- in cancer cells versus cellular
non-cancer cells COMP Increased expression NP_000086.2 2 Extra- in
cancer cells versus cellular non-cancer cells CXCL11 Increased
expression NP_005400.1 2 Extra- in cancer cells versus cellular
non-cancer cells CXCL14 Increased expression NP_004878.2 2 Extra-
in cancer cells versus cellular non-cancer cells CXCL9 Increased
expression NP_002407.1 2 Extra- in cancer cells versus cellular
non-cancer cells DHRS8 Increased expression NP_057329.1 2 Extra- in
cancer cells versus cellular non-cancer cells ITGBL1 Increased
expression NP_004782.1 2 Extra- in cancer cells versus cellular
non-cancer cells LOX Increased expression NP_002308.2 2 Extra- in
cancer cells versus cellular non-cancer cells MUC1 Increased
expression NP_ 2 Extra- in cancer cells versus 001018016.1 cellular
non-cancer cells NP_ 001018017.1 NP_ 001018021.1 NP_002447.4 OR51E1
Increased expression NP_689643.1 2 Extra- in cancer cells versus
cellular non-cancer cells PCSK6 Increased expression NP_002561.1 2
Extra- in cancer cells versus NP_612192.1 cellular non-cancer cells
NP_612193.1 NP_612194.1 NP_612195.1 NP_612196.1 NP_612197.1
NP_612198.2 RPL22L1 Increased expression XP_498952.2 2 Extra- in
cancer cells versus XP_940025.1 cellular non-cancer cells
XP_947405.1 XP_950994.1 C1orf64 Increased expression NP_849162.1 3
Extra- in cancer cells versus cellular non-cancer cells CCL19
Increased expression NP_006265.1 3 Extra- in cancer cells versus
cellular non-cancer cells NRP1 Increased expression NP_ 3 Extra- in
cancer cells versus 001019799.1 cellular non-cancer cells NP_
001019800.1 NP_003864.3 SFTPA2 Increased expression NP_008857.1 3
Extra- in cancer cells versus cellular non-cancer cells CDH10
Increased expression NP_006718.2 1 Membrane- in cancer cells versus
associated non-cancer cells CDH7 Increased expression NP_004352.2 1
Membrane- in cancer cells versus NP_387450.1 associated non-cancer
cells CHRM3 Increased expression NP_000731.1 1 Membrane- in cancer
cells versus associated non-cancer cells FZD8 Increased expression
NP_114072.1 1 Membrane- in cancer cells versus associated
non-cancer cells GJB1 Increased expression NP_000157.1 1 Membrane-
in cancer cells versus associated non-cancer cells MS4A8B Increased
expression NP_113645.1 1 Membrane- in cancer cells versus
associated non-cancer cells OR51E2 Increased expression NP_110401.1
1 Membrane- in cancer cells versus associated non-cancer cells
SLC43A1 Increased expression NP_003618.1 1 Membrane- in cancer
cells versus associated non-cancer cells TMEM45B Increased
expression NP_620143.1 1 Membrane- in cancer cells versus
associated non-cancer cells FAM77C Increased expression NP_078798.1
1 Membrane- in cancer cells versus associated non-cancer cells
GPR116 Increased expression NP_056049.3 1 Membrane- in cancer cells
versus associated non-cancer cells GRIN3A Increased expression
NP_597702.1 1 Membrane- in cancer cells versus associated
non-cancer cells HPN Increased expression NP_002142.1 2 Membrane-
in cancer cells versus NP_892028.1 associated non-cancer cells
PCDHB10 Increased expression NP_061753.1 2 Membrane- in cancer
cells versus associated non-cancer cells PCDHGA4 Increased
expression NP_061740.1 2 Membrane- in cancer cells versus
NP_114442.1 associated non-cancer cells PRG-3 Increased expression
NP_060223.2 2 Membrane- in cancer cells versus NP_997182.1
associated non-cancer cells RET Increased expression NP_065681.1 2
Membrane- in cancer cells versus NP_066124.1 associated non-cancer
cells ACPP High-level, NP_001090.2 1 Extra- prostate-preferential
cellular expression FAM61B High-level, NP_653304.1 1 Extra-
prostate-preferential cellular expression MSMB High-level,
NP_002434.1 1 Extra- prostate-preferential NP_619540.1 cellular
expression PGLS High-level, NP_036220.1 1 Extra-
prostate-preferential cellular expression RBM35A High-level, NP_ 1
Extra- prostate-preferential 001030087.1 cellular expression
NP_060167.2 TMPRSS2 High-level, NP_005647.2 1 Extra-
prostate-preferential cellular expression LOC284591 High-level,
XP_932207.1 2 Extra- prostate-preferential XP_941863.1 cellular
expression ADAMTS8 High-level, NP_008968.3 2 Extra-
prostate-preferential cellular expression EFNA4 High-level,
NP_005218.1 3 Extra- prostate-preferential NP_872631.1 cellular
expression NP_872632.1 KAZALD1 High-level, NP_112191.2 3 Extra-
prostate-preferential cellular expression SEMA3F High-level,
NP_004177.2 3 Extra- prostate-preferential cellular expression UCN
High-level, NP_003344.1 3 Extra- prostate-preferential cellular
expression PRAC2 High-level, Entrez Gene 3 Extra-
prostate-preferential 360205 cellular expression
TABLE-US-00003 TABLE 3 Nucleic acids encoding extracellular
polypeptides that can be used in combination with one or more
polypeptides encoded by nucleic acids listed in Table 2 to identify
prostate cancer. Nucleic RefSeq Acid Protein Local- Symbol
Selection Process Identifier Category ization CRISP3 Increased
expression NP_006052.1 1 Extra- in cancer cells versus cellular
non-cancer cells AMACR Increased expression NP_055139.4 3 Extra- in
cancer cells versus NP_976316.1 cellular non-cancer cells KLK2
High-level , prostate- NP_001002231.1 1 Extra- preferential
expression NP_001002232.1 cellular NP_005542.1 KLK3 High-level ,
prostate- NP_001025218.1 1 Extra- preferential expression
NP_001025219.1 cellular NP_001025220.1 NP_001025221.1 NP_001639.1
KLK4 High-level, prostate- NP_004908.2 2 Extra- preferential
expression cellular PSCA High-level, prostate- NP_005663.1 2 Extra-
preferential expression cellular
TABLE-US-00004 TABLE 4 Nucleic acids encoding extracellular or
membrane-associated polypeptides that are differentially expressed
in cancerous and non-cancerous prostate epithelial cells. Nucleic
RefSeq Acid Protein Local- Symbol Selection Process Identifier
Category ization APOC1 Increased expression NP_001636.1 1 Extra- in
cancer cells versus cellular non-cancer cells ASPN Increased
expression NP_060150.3 1 Extra- in cancer cells versus cellular
non-cancer cells BCMP11 Increased expression NP_789783.1 1 Extra-
in cancer cells versus cellular non-cancer cells C20orf102
Increased expression NP_542174.1 1 Extra- in cancer cells versus
cellular non-cancer cells COL2A1 Increased expression NP_001835.2 1
Extra- in cancer cells versus NP_149162.1 cellular non-cancer cells
F5 Increased expression NP_000121.1 1 Extra- in cancer cells versus
cellular non-cancer cells HLA-DMB Increased expression NP_002109.1
1 Extra- in cancer cells versus cellular non-cancer cells LRRN1
Increased expression NP_065924.2 1 Extra- in cancer cells versus
cellular non-cancer cells MMP26 Increased expression NP_068573.2 1
Extra- in cancer cells versus cellular non-cancer cells NRN1
Increased expression NP_057672.1 1 Extra- in cancer cells versus
cellular non-cancer cells OGDHL Increased expression NP_060715.1 1
Extra- in cancer cells versus cellular non-cancer cells PLA1A
Increased expression NP_056984.1 1 Extra- in cancer cells versus
cellular non-cancer cells PLA2G7 Increased expression NP_005075.2 1
Extra- in cancer cells versus cellular non-cancer cells SFRP4
Increased expression NP_003005.1 1 Extra- in cancer cells versus
cellular non-cancer cells ALDH3B2 Increased expression NP_000686.2
2 Extra- in cancer cells versus NP_ cellular non-cancer cells
001026786.1 APOF Increased expression NP_001629.1 2 Extra- in
cancer cells versus cellular non-cancer cells B3Gn-T6 Increased
expression NP_619651.2 2 Extra- in cancer cells versus cellular
non-cancer cells C4A///C4B Increased expression NP_ 2 Extra- in
cancer cells versus 001002029.1 cellular non-cancer cells
NP_009224.2 COL9A2 Increased expression NP_001843.1 2 Extra- in
cancer cells versus cellular non-cancer cells COMP Increased
expression NP_000086.2 2 Extra- in cancer cells versus cellular
non-cancer cells CXCL11 Increased expression NP_005400.1 2 Extra-
in cancer cells versus cellular non-cancer cells CXCL14 Increased
expression NP_004878.2 2 Extra- in cancer cells versus cellular
non-cancer cells CXCL9 Increased expression NP_002407.1 2 Extra- in
cancer cells versus cellular non-cancer cells DHRS8 Increased
expression NP_057329.1 2 Extra- in cancer cells versus cellular
non-cancer cells ITGBL1 Increased expression NP_004782.1 2 Extra-
in cancer cells versus cellular non-cancer cells LOX Increased
expression NP_002308.2 2 Extra- in cancer cells versus cellular
non-cancer cells MUC1 Increased expression NP_ 2 Extra- in cancer
cells versus 001018016.1 cellular non-cancer cells NP_ 001018017.1
NP_ 001018021.1 NP_002447.4 OR51E1 Increased expression NP_689643.1
2 Extra- in cancer cells versus cellular non-cancer cells PCSK6
Increased expression NP_002561.1 2 Extra- in cancer cells versus
NP_612192.1 cellular non-cancer cells NP_612193.1 NP_612194.1
NP_612195.1 NP_612196.1 NP_612197.1 NP_612198.2 RPL22L1 Increased
expression XP_498952.2 2 Extra- in cancer cells versus XP_940025.1
cellular non-cancer cells XP_947405.1 XP_950994.1 C1orf64 Increased
expression NP_849162.1 3 Extra- in cancer cells versus cellular
non-cancer cells CCL19 Increased expression NP_006265.1 3 Extra- in
cancer cells versus cellular non-cancer cells NRP1 Increased
expression NP_ 3 Extra- in cancer cells versus 001019799.1 cellular
non-cancer cells NP_ 001019800.1 NP_003864.3 SFTPA2 Increased
expression NP_008857.1 3 Extra- in cancer cells versus cellular
non-cancer cells CDH10 Increased expression NP_006718.2 1 Membrane-
in cancer cells versus associated non-cancer cells CDH7 Increased
expression NP_004352.2 1 Membrane- in cancer cells versus
NP_387450.1 associated non-cancer cells CHRM3 Increased expression
NP_000731.1 1 Membrane- in cancer cells versus associated
non-cancer cells FZD8 Increased expression NP_114072.1 1 Membrane-
in cancer cells versus associated non-cancer cells GJB1 Increased
expression NP_000157.1 1 Membrane- in cancer cells versus
associated non-cancer cells MS4A8B Increased expression NP_113645.1
1 Membrane- in cancer cells versus associated non-cancer cells
OR51E2 Increased expression NP_110401.1 1 Membrane- in cancer cells
versus associated non-cancer cells SLC43A1 Increased expression
NP_003618.1 1 Membrane- in cancer cells versus associated
non-cancer cells TMEM45B Increased expression NP_620143.1 1
Membrane- in cancer cells versus associated non-cancer cells FAM77C
Increased expression NP_078798.1 2 Membrane- in cancer cells versus
associated non-cancer cells GPR116 Increased expression NP_056049.3
2 Membrane- in cancer cells versus associated non-cancer cells
GRIN3A Increased expression NP_597702.1 2 Membrane- in cancer cells
versus associated non-cancer cells HPN Increased expression
NP_002142.1 2 Membrane- in cancer cells versus NP_892028.1
associated non-cancer cells PCDHB10 Increased expression
NP_061753.1 2 Membrane- in cancer cells versus associated
non-cancer cells PCDHGA4 Increased expression NP_061740.1 2
Membrane- in cancer cells versus NP_114442.1 associated non-cancer
cells PRG-3 Increased expression NP_060223.2 2 Membrane- in cancer
cells versus NP_997182.1 associated non-cancer cells RET Increased
expression NP_065681.1 2 Membrane- in cancer cells versus
NP_066124.1 associated non-cancer cells
Other Embodiments
[0068] It is to be understood that while the invention has been
described in conjunction with the detailed description thereof, the
foregoing description is intended to illustrate and not limit the
scope of the invention, which is defined by the scope of the
appended claims. Other aspects, advantages, and modifications are
within the scope of the following claims.
Sequence CWU 1
1
63113PRTHomo sapiens 1Ser Tyr Asp Leu Asp Pro Gly Ala Gly Ser Leu
Glu Ile1 5 10210PRTHomo sapiens 2Ile Gln Asp Ile Asn Asp Asn Glu
Pro Lys1 5 10318PRTHomo sapiens 3Gly Glu Gln Gly Pro Pro Gly Ile
Pro Gly Pro Gln Gly Leu Pro Gly1 5 10 15Val Lys413PRTHomo sapiens
4Glu Leu Gln Glu Thr Asn Ala Ala Leu Gln Asp Val Arg1 5
10512PRTHomo sapiens 5Leu Val Pro Asn Pro Gly Gln Glu Asp Ala Asp
Arg1 5 10613PRTHomo sapiens 6Asn Gln Gly Thr Ser Asp Phe Leu Pro
Ser Arg Pro Arg1 5 10710PRTHomo sapiens 7Glu Pro Pro Ala Ala Pro
Gly Ala Trp Arg1 5 10810PRTHomo sapiens 8Val Ala Glu Asn Glu Asn
Pro Gly Ala Arg1 5 10918PRTHomo sapiens 9Gly Ala Asn Gly Asp Pro
Gly Arg Pro Gly Glu Pro Gly Leu Pro Gly1 5 10 15Ala Arg1016PRTHomo
sapiens 10Ala Gly Glu Pro Gly Leu Gln Gly Pro Ala Gly Pro Pro Gly
Glu Lys1 5 10 151115PRTHomo sapiens 11Gly Pro Pro Gly Pro Gln Gly
Pro Ala Gly Glu Gln Gly Pro Arg1 5 10 151219PRTHomo sapiens 12Ala
Gly Pro Asp Gly Pro Asp Gly Lys Pro Gly Ile Asp Gly Leu Thr1 5 10
15Gly Ala Lys1315PRTHomo sapiens 13Gly Ile Leu Gly Asp Pro Gly His
Gln Gly Lys Pro Gly Pro Lys1 5 10 151417PRTHomo sapiens 14Ala Thr
Asp Pro Asp Glu Gly Ala Asn Gly Asp Val Thr Tyr Ser Phe1 5 10
15Arg1512PRTHomo sapiens 15His Leu Thr Pro Val Thr Leu Glu Leu Gly
Gly Lys1 5 101614PRTHomo sapiens 16Ser Gly Val Gln Gln Leu Ile Gln
Tyr Tyr Gln Asp Gln Lys1 5 101717PRTHomo sapiens 17Leu Tyr Leu Ser
His Asn Gln Leu Ser Glu Ile Pro Leu Asn Leu Pro1 5 10
15Lys1819PRTHomo sapiens 18Ala Leu Glu Ile Leu Gln Glu Glu Asp Leu
Ile Asp Glu Asp Asp Ile1 5 10 15Pro Val Arg1919PRTHomo sapiens
19Ala Leu Glu Ile Leu Gln Glu Glu Asp Leu Ile Asp Glu Asp Asp Ile1
5 10 15Pro Val Arg2017PRTHomo sapiens 20Gly His Leu Phe Leu Gln Thr
Asp Gln Pro Ile Tyr Asn Pro Gly Gln1 5 10 15Arg2113PRTHomo sapiens
21Gly Leu Glu Glu Glu Leu Gln Phe Ser Leu Gly Ser Lys1 5
102219PRTHomo sapiens 22Asn Tyr Tyr Ile Ala Ala Glu Glu Ile Ser Trp
Asp Tyr Ser Glu Phe1 5 10 15Val Gln Arg2314PRTHomo sapiens 23Ser
Tyr Thr Ile His Tyr Ser Glu Gln Gly Val Glu Trp Lys1 5
102419PRTHomo sapiens 24Asp Gly Leu Asp Ile Gln Leu Pro Gly Asp Asp
Pro His Ile Ser Val1 5 10 15Gln Phe Arg2511PRTHomo sapiens 25His
His Val Leu His Asp Gln Glu Val Asp Arg1 5 102617PRTHomo sapiens
26Gln Tyr Leu Leu Leu Asp Ser His Thr Gly Asn Leu Leu Thr Asn Glu1
5 10 15Lys2712PRTHomo sapiens 27Asp Ile Asn Asp His Ala Pro Val Phe
Gln Asp Lys1 5 102821PRTHomo sapiens 28Ile Leu Glu Asp Gln Glu Glu
Asn Pro Leu Pro Ala Ala Leu Val Gln1 5 10 15Pro His Thr Gly Lys
202924PRTHomo sapiens 29Phe Asn Leu Asp Leu Thr His Pro Val Glu Asp
Gly Ile Phe Asp Ser1 5 10 15Gly Asn Phe Glu Gln Phe Leu Arg
20309PRTHomo sapiens 30Tyr Glu Ala Ala Val Pro Asp Pro Arg1
53111PRTHomo sapiens 31Glu Thr Gly Leu Glu Thr Ser Ser Gly Gly Lys1
5 103211PRTHomo sapiens 32Asp Ile Ile Pro Glu Thr Leu Phe Ile Pro
Arg1 5 103311PRTHomo sapiens 33Val Glu Ala Glu Asn Thr His Val Asp
Pro Arg1 5 103410PRTHomo sapiens 34Ser Ser His Pro Glu Thr Tyr Gln
Gln Arg1 5 10359PRTHomo sapiens 35Thr Val Glu Ser Leu Pro Asn Leu
Arg1 53611PRTHomo sapiens 36Ile Asp Asn Pro His Ile Thr Tyr Thr Ala
Arg1 5 103710PRTHomo sapiens 37Gly Thr Thr Gly Thr Gln Leu Asn Gly
Arg1 5 10387PRTHomo sapiens 38Trp Leu Gln Gln Glu Val Lys1
53917PRTHomo sapiens 39Ala Glu Gly Gln Trp Thr Leu Glu Ile Gln Asp
Leu Pro Ser Gln Val1 5 10 15Arg4013PRTHomo sapiens 40Gly Leu Pro
Trp Gln Ser Ser Asp Gln Asp Ile Ala Arg1 5 104117PRTHomo sapiens
41Asp Lys Leu Arg Lys Glu Ser Lys Asn Leu Asn Ile Gln Gly Ser Lys1
5 10 15Phe4211PRTHomo sapiens 42Ile Glu Ala Leu Ser Ser Ala Leu Gln
Ile Phe1 5 104316PRTHomo sapiens 43Leu Gly Ser Pro Leu Arg Gly Gly
Ser Ser Leu Arg His Val Val Tyr1 5 10 154412PRTHomo sapiens 44Leu
Ser Glu Pro Ala Glu Leu Thr Asp Ala Val Lys1 5 104512PRTHomo
sapiens 45His Ser Gln Pro Trp Gln Val Leu Val Ala Ser Arg1 5
10469PRTHomo sapiens 46Glu Thr His Ala Ser Ala Pro Val Lys1
54713PRTHomo sapiens 47Gly Leu Gly Ala Thr Thr His Pro Thr Ala Ala
Val Lys1 5 104813PRTHomo sapiens 48Gln Leu Cys Ala Pro Pro Asp Gln
Pro Trp Val Glu Arg1 5 104916PRTHomo sapiens 49Glu Ile Pro Ala Trp
Val Pro Glu Asp Pro Ala Ala Gln Ile Thr Lys1 5 10 155010PRTHomo
sapiens 50Thr Pro Asp Val Ser Ser Ala Leu Asp Lys1 5 105114PRTHomo
sapiens 51Thr Thr Asn Ile Gln Gly Ile Asn Leu Leu Phe Ser Ser Arg1
5 105216PRTHomo sapiens 52Glu Ile Pro Ala Trp Val Pro Phe Asp Pro
Ala Ala Gln Ile Thr Lys1 5 10 155316PRTHomo sapiens 53Glu Leu Pro
Ala Ala Val Ala Pro Ala Gly Pro Ala Ser Leu Ala Arg1 5 10
155421PRTHomo sapiens 54Pro Leu Pro Glu Pro Leu Thr Val Gln Leu Leu
Thr Val Pro Gly Glu1 5 10 15Val Phe Pro Pro Lys 205512PRTHomo
sapiens 55Val Ala Ile Gly Gly Gln Ser Asn Glu Ser Asp Arg1 5
105611PRTHomo sapiens 56Leu Leu Pro Ala Leu Gln Ser Thr Ile Thr
Arg1 5 105715PRTHomo sapiens 57Gln Gly Gly Val Asn Ala Thr Gln Val
Leu Ile Gln His Leu Arg1 5 10 155813PRTHomo sapiens 58Leu Glu Gly
His Gly Asp Pro Leu His Glu Glu Val Lys1 5 105912PRTHomo sapiens
59Asp Leu Gly Leu Ala Glu Gly Glu Leu Ala Ala Arg1 5 106014PRTHomo
sapiens 60Ser Ile Leu Gln Gly Gln Pro Tyr Phe Ser Val Glu Pro Lys1
5 106114PRTHomo sapiens 61Phe Leu Ser Leu Gly Pro Phe Ser Asp Thr
Thr Thr Val Lys1 5 106222PRTHomo sapiens 62Ile Ala Val Ile Gly His
Ser Phe Gly Gly Ala Thr Val Ile Gln Thr1 5 10 15Leu Ser Glu Asp Gln
Arg 206310PRTHomo sapiens 63Val Gly Asp Thr Leu Asn Leu Asn Leu
Arg1 5 10
* * * * *