microRNA Profiling in Clear Cell Renal Cell Carcinoma: Biomarker Discover and Identification of Potential Controls and Consequences of miRNA Dysregulation.
Nicole MA White, Tian Tian Bao, Jorg Grigull, Youssef M Youssef, Andrew Girgis, Maria Diamandis, Eman Fatoohi, Maged Metias, R John Honey, Robert Stewart, Kenneth T Pace, George A Bjarnason, George M Yousef. Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada; University of Toronto, ON, Canada; York University, Toronto, ON, Canada; St. Michael's Hospital, Toronto, ON, Canada; Sunnybrook Odette Cancer Center, Toronto, ON, Canada
Background: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Currently, there are no biomarkers for the diagnostic, prognostic, or predictive applications in RCC. MicroRNAs (miRNAs) are short non protein-coding RNAs that negatively regulate gene expression and have been shown to be potential biomarkers for cancer.
Design: We analyzed a total of 70 matched pairs of clear cell RCC (ccRCC) and normal kidney tissues from the same patients by microarray analysis and validated our results by quantitative real time PCR. We also did extensive bioinformatic analyses to explore the role and regulation of miRNAs in ccRCC.
Results: We identified 166 miRNAs significantly dysregulated in ccRCC. MiR-122, miR-155 and miR-210 had the highest fold changes of overexpression while miR-200c, miR-335, and miR-218 were the most downregulated. Combinatorial analysis of previously reported miRNAs dysregulated in RCC showed an overlap of many miRNAs. Extensive target prediction analysis showed many miRNAs were predicted to target a number of genes involved in RCC pathogenesis. MiRNA dysregulation in RCC can be attributed in part, to chromosomal aberrations, the co-regulation of miRNA clusters, and co-expression with host genes. We also correlated miRNA expression with clinical characteristics and found miR-155 expression was correlated with ccRCC tumor size.
Conclusions: Our analysis showed that a number of miRNAs are dysregulated in ccRCC and may contribute to kidney cancer pathogenesis by targeting key molecules. We identified mechanisms that may contribute to miRNA dysregulation in ccRCC. Dysregulated miRNAs represent potential biomarkers and therapeutic targets for kidney cancer.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 105, Wednesday Morning