Gene expression profile associated with prostate cancer
Using an RT-PCR platform, detection of gene transcripts highly expressed in prostate tissue and expressed in peripheral blood mononuclear cells (PBMC) from patients with mCRPC can provide a more reliable and robust prediction of poor overall survival than that of CTC enumeration in mCRPC. Disclosed is the identification of five genes, KLK3, KLK2, HOXB13, GHRL2 and FOXA1, the detection of two (2) or more transcripts of which predicts overall poor survival. The test is performed on blood samples that have been collected in collection tubes that stabilize intracellular RNA, require minimal on-site processing and can be easily stored and shipped for subsequent extraction of total RNA from whole blood for RT-PCR.
1. A method of identifying overall survival of a metastatic castrate-resistant prostate cancer patient, the method comprising:
(a) assaying a blood sample from the patient to detect the concentration of lactate dehydrogenase (LDH) in the blood sample, wherein the concentration of LDH detected is at least 250 U/liter;
(b) contacting RNA from a stabilized blood sample from the patient with a set of oligonucleotide primers, wherein the set of oligonucleotide primers consists of at least one pair of oligonucleotide primers for each of genes KLK3, KLK2, HOXB13, GHRL2 and FOXA1;
(c) performing PCR on said RNA to produce amplified RNA expression products;
(d) detecting the presence of an amplified RNA expression product of any of KLK3, KLK2, HOXB13, GHRL2 and FOXA1 in the stabilized blood sample from the patient; and
(e) identifying the patient as one who will have:
(i) overall survival of about 15 to 18 months when an RNA expression product of one of KLK3, KLK2, HOXB13, GHRL2 and FOXA1 is detected in the patient's stabilized blood sample;
(ii) overall survival of about 11 to 15 months when RNA expression products of two of KLK3, KLK2, HOXB13, GHRL2 and FOXA1 are detected in the patient's stabilized blood sample; or
(iii) overall survival of about 36 to 42 months when no RNA expression products of any of KLK3, KLK2, HOXB13, GHRL2 and FOXA1 are detected in the patient's stabilized blood sample.
2. A method of predicting overall survival of a metastatic castrate-resistant prostate cancer patient, the method comprising:
(a) assaying a blood sample from the patient to detect the concentration of lactate dehydrogenase (LDH) in the blood sample, wherein the concentration of LDH detected is at least 250 U/liter;
(b) performing a nucleic acid detection assay on a stabilized blood sample from the patient to determine the quantity of RNA or cDNA expression products of the KLK3, KLK2, HOXB13, GHRL2 and FOXA1 genes in the stabilized blood sample; and
(c) predicting:
(i) overall survival of about 15 to 18 months when an RNA or cDNA expression product of one of KLK3, KLK2, HOXB13, GHRL2 and FOXA1 is detected in the patient sample;
(ii) overall survival of about 11 to 15 months when an RNA or cDNA expression product of two of KLK3, KLK2, HOXB13, GHRL2 and FOXA1 are detected in the patient sample; or
(iii) overall survival of about 36 to 42 months when no expression RNA or cDNA products of any of KLK3, KLK2, HOXB13, GHRL2 and FOXA1 are detected in the patient sample.
3. The method of claim 1 , wherein said PCR comprises real time PCR.