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Am J Transl Res 2013;5(2):200-211
Original Article
Comprehensive molecular oncogenomic profiling and miRNA analysis
of prostate cancer
Seema Sethi, Dejuan Kong, Sue Land, Gregory Dyson, Wael A Sakr, Fazlul H Sarkar
Departments of Pathology & Oncology, and division of Statistics, Karmanos Cancer Institute, Wayne State
University School of Medicine and Detroit Medical Center, Detroit, MI
Received January 24, 2013; Accepted February 19, 2013; Epub March 28, 2013; Published April 8, 2013
Abstract: 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 (AJTR1301007).
Keywords: Molecular, oncogenomic, miRNA, profiling, prostate cancer
Address correspondence to: Dr. Fazlul H Sarkar, Department of Pathology, Karmanos Cancer Institute, Wayne
State University School of Medicine, 740 Hudson Webber Cancer Research Center, 4100 John R, Detroit, MI
48201. Tel: 313-576-8327; Fax: 313-576-8389; E-mail: fsarkar@med.wayne.edu
Original Article
Comprehensive molecular oncogenomic profiling and miRNA analysis
of prostate cancer
Seema Sethi, Dejuan Kong, Sue Land, Gregory Dyson, Wael A Sakr, Fazlul H Sarkar
Departments of Pathology & Oncology, and division of Statistics, Karmanos Cancer Institute, Wayne State
University School of Medicine and Detroit Medical Center, Detroit, MI
Received January 24, 2013; Accepted February 19, 2013; Epub March 28, 2013; Published April 8, 2013
Abstract: 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 (AJTR1301007).
Keywords: Molecular, oncogenomic, miRNA, profiling, prostate cancer
Address correspondence to: Dr. Fazlul H Sarkar, Department of Pathology, Karmanos Cancer Institute, Wayne
State University School of Medicine, 740 Hudson Webber Cancer Research Center, 4100 John R, Detroit, MI
48201. Tel: 313-576-8327; Fax: 313-576-8389; E-mail: fsarkar@med.wayne.edu
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