Comprehensive molecular oncogenomic profiling and miRNA analysis of prostate cancer.

This study was focused on molecular profiling of prostate cancer (PCa) using scant amounts of both frozen and formalin-fixed paraffin-embedded (FFPE) PCa tissue specimens. DNA and RNA were extracted and interrogated for: (1) whole-genome gene expression profiling, (2) miRNA expression analysis, (3) SNP analysis, and (4) mutation analysis. Data was statistically analyzed and correlated with clinical and pathologic variables. Expression profiling of 47,224 genes revealed 74 genes that were significant in predicting high tumor grade in PCa (p<0.0001). These were involved in many cellular processes as analyzed by Ingenuity Pathway Analysis (IPA). Using novel high throughput technologies, we identified a specific oncogenomic and miRNA signatures showing loss of miR-34 expression. Interestingly, p53 was at the center hub of the signaling pathways, and the loss of miR-34a expression was consistent with the central role of p53 in PCa. Analysis of 731,442 SNP's, revealed 638 SNP's that were significant in predicting high tumor grade (p<0.0001; logistic regression analysis). We also found, for the first time, a novel hot spot mutation in MET oncogene, variant T992I, suggesting that our findings would be useful in further defining the role of specific regulatory genes and miRNAs in the pathological evolution of PCa, and could also have potential clinical utility in improving diagnostic accuracy, refining prognostic and predictive capabilities and may serve as therapeutic targets.