Quantitative analysis of a panel of gene expression in prostate cancer——with emphasis on NPY expression analysis

Objective: To investigate molecular alterations associating with prostate carcinoma progression and potentially provide information toward more accurate prognosis/diagnosis. Methods: A set of laser captured microdissected (LCM) speci- mens from 300 prostate cancer (PCa) patients undergoing radical prostatectomy (RP) were defined. Ten patients representing "aggressive" PCa, and 10 representing "non-aggressive" PCa were selected based on prostate-specific antigen (PSA) recurrence, Gleason score, pathological stage and tumor cell differentiation, with matched patient age and race between the two groups. Normal and neoplastic prostate epithelial cells were collected with LCM from frozen tissue slides obtained from the RP specimens. The expressions of a panel of genes, including NPY, PTEN, AR, AMACR, DD3, and GSTP1, were measured by quantitative real-time RT-PCR (TaqMan), and correlation was analyzed with clinicopathological features. Results: The expressions of AMACR and DD3 were consistently up-regulated in cancer cells compared to benign prostate epithelial cells in all PCa patients, whereas GSTP1 expression was down regulated in each patient. NPY, PTEN and AR exhibited a striking difference in their expression patterns between aggressive and non-aggressive PCas (P=0.0203, 0.0284, and 0.0378, respectively, Wilcoxon rank sum test). The lower expression of NPY showed association with "aggressive" PCas based on a larger PCa patient cohort analysis (P=0.0037, univariate generalized linear model (GLM) analysis). Conclusion: Despite widely noted heterogeneous nature of PCa, gene ex- pression alterations of AMACR, DD3, and GSTP1 in LCM-derived PCa epithelial cells suggest for common underlying mecha- nisms in the initiation of PCa. Lower NPY expression level is significantly associated with more aggressive clinical behavior of PCa; PTEN and AR may have potential in defining PCa with aggressive clinical behavior. Studies along these lines have potential to define PCa-associated gene expression alterations and likely co-regulation of genes/pathways critical in the biology of PCa onset/progression.

Long noncoding RNA-mediated activation of androgen receptor in prostate cancer

Remarkable progress has been made in molecular characterization of prostate cancer （PCa） with continued innovations in high throughput technologies evaluating human cancer？-3 Since the completion of the Human Genome Project it has been estimated that only about 1.5%-2% of our genome codes for proteins. Various genome-wide approaches, e.g. the ENCODE project, revealed that a much larger percent of the genome is transcribed as non-protein coding （nc） RNA, including long noncoding （lnc） RNA （over 200bps long）. Although the biological roles of IncRNA （the ＇dark matter of the genome＇） are not nearly as well-understood as the protein coding mRNAs, it is increasingly clear that they play important roles in almost every aspects of biology, including cancer biology.4＇5 This is exemplified by recent genome-wide association studies revealing that over 80% of cancer-associated single nucleotide polymorphisms （SNPs） are in noncoding regions of the genome.

Highlights from the prostate cancer genome report

Prostate cancer （CAP） is the second most frequently diagnosed cancer of men worldwide （899 000 new cases, 13.6% of the total）, with nearly 75% of the registered cases occurring in developed countries （644 000 cases）.1 Blood prostate-specific antigen test has revolutionized the early detection of CaP and organ-confined CaP is effectively managed by state-of-the-art treatments including radical prostatectomy or radiation therapy.2 In the past decade, tremendous progress has also been made in our understanding of the biology and common genomic alterations in CaP.3＇4 New molecular marker assays have promise in improving CaP diagnosis.5-8 Despite these advances, major challenges remain with our ability to distinguish indolent cancers from the more aggressive cancers detected early due to widely used prostate-specific antigen test. Furthermore, development of molecular stratification of CaP for targeted and more effective therapies is critically needed.