PROSTATE CANCER SURVIVAL AND RECURRENCE
The disclosure includes the identification and use of gene expression profiles, or patterns, with clinical relevance to prostate cancer. In particular, the disclosure is based on the identities of genes that are correlated with patient survival and prostate cancer recurrence. The gene expression profiles may be embodied in nucleic acid expression, protein expression, or other expression formats and used to predict the survival of subjects afflicted with prostate cancer and to predict prostate cancer recurrence. The profiles may also be used in the study and/or diagnosis of prostate cancer cells and tissue as well as for the study and/or determination of prognosis of a patient. When used for diagnosis or prognosis, the profiles may be used to determine the treatment of prostate cancer based upon probable life expectancy and cancer recurrence and/or metastasis.
1 . A method to determine the cancer recurrence and/or survival outcome, or prognosis, of a prostate cancer afflicted subject, said method comprising assaying a sample comprising prostate cancer cells of said subject for the expression levels of genes, wherein the expression levels are correlated with
a low risk of cancer recurrence and/or metastasis,
a high risk of cancer recurrence and/or metastasis, or
elevated PSA levels after about one year of prostatectomy.
2 . A method to determine the risk of prostate cancer recurrence and/or metastasis in a subject, said method comprising
assaying a sample comprising prostate cancer cells from said subject for the expression levels of two or more genes selected from Gene Nos: 1 to 362 in FIGS. 14 and 15 ,
comparing the expression level of each gene, or the aggregated expression level, with the mean or median expression values in prostate cancer cells, and
determining the risk of prostate cancer recurrence and/or metastasis in said subject
wherein the expression levels are correlated with
a low risk of cancer recurrence and/or metastasis, or
a high risk of cancer recurrence and/or metastasis.
3 . The method of claim 2 wherein said method further comprises selecting a treatment for a subject with the determined cancer recurrence and/or survival outcome.
4 . The method of claim 2 wherein said assaying comprises preparing RNA from said sample.
5 . The method of claim 4 wherein said RNA is used for PCR.
6 . The method of claim 4 wherein said assaying comprises using an array.
7 . The method of claim 2 wherein said sample is dissected from tissue removed during prostatectomy.
8 . The method of claim 5 wherein said PCR is RT-PCR, optionally real time RT-PCR.
9 . The method of claim 2 wherein said expression levels are correlation is with a p value of <0.0001.
10 . The method of claim 2 wherein said sample comprises isolated prostate cancer cells.
11 . A method to determine therapeutic treatment for a prostate cancer patient after prostatectomy, said method comprising
determining a cancer recurrence and/or survival outcome for said patient by assaying a sample of prostate cancer cells from said patient for the expression levels of genes, wherein the expression levels are correlated with
a low risk of cancer recurrence or metastasis,
a high risk of cancer recurrence or metastasis, or
elevated PSA levels after about one year of prostatectomy; and
selecting a treatment for a patient with such a cancer recurrence and/or survival outcome.
12 . The method of claim 3 wherein said treatment comprises chemotherapy.
13 . The method of claim 3 wherein said treatment comprises radiation therapy.
14 . The method of claim 1 further comprising
i) determining the grade of prostate cancer in said sample,
ii) determining the stage of prostate cancer in said sample, or
iii) both;
wherein i), ii) or both i) and ii) are optionally performed before determining the risk of prostate cancer recurrence and/or metastasis in said subject.
15 . The method of claim 14 wherein determining prostate cancer grade comprises determination of a Gleason Score.
16 . The method of claim 14 wherein determining prostate cancer stage comprises determination of the AJCC stage.
17 . The method of claim 14 wherein the method comprises determining prostate cancer grade by a Gleason Score and determining prostate cancer stage according to AJCC stage to produce a multivariate analysis for determining the risk of prostate cancer recurrence and/or metastasis in said subject.
18 . The method of claim 2 further comprising determining prostate serum antigen (PSA) levels in said subject, optionally before a prostatectomy which is used to provide said sample comprising prostate cancer cells.
19 . The method of claim 2 wherein expression levels of 4 or more, such as 6 or more, 8 or more, 10 or more, 12 or more, 14 or more, 16 or more, 18 or more, 20 or more, 22 or more, 24 or more, 26 or more, 28 or more, 30 or more, 32 or more, 34 or more, 36 or more, 38 or more, 40 or more, 45 or more, 50 or more, 55 or more, 60 or more, 65 or more, 70 or more, or 92 or more genes are assayed.
20 . The method of claim 2 wherein said assaying comprises determining the expression level of Gene No. 1, optionally via use of SEQ ID NO: 1 as a probe.