Clinical Significance of miR-21 in Renal Cell Carcinoma.
Hala Faragalla, Youssef Youssef, Bishov Kahalil, Nicole MA White, Salvador Mejia-Guerrero, Cathy Streutker, Michael Jewett, Georg Bjarnason, Linda Sugar, Magdy I Attalah, George M Yousef. Li Ka Shing Knowledge Institue St. Michael's Hosptial, Toronto, ON, Canada; Princess Margaret Hospital, Toronto, ON, Canada; Sunnybrook Health Sciences Center, Toronto, ON, Canada; University of Toronto, ON, Canada
Background: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Increasing evidence suggests that microRNAs (miRNAs) are dysregulated in RCC and are important players in RCC pathogenesis. MiR-21 is a known oncogene with tumor promoting effect in many types of cancer. The aim of this study was to examine miR-21 expression in RCC and to identify its potential clinical significance.
Design: We analyzed miR-21 expression in 105 cases of RCC and eight normal kidneys. More specifically, we analyzed 65 primary clear cell RCCs, 10 papillary RCCs, 10 chromophobe RCCs, 10 oncocytomas and 10 metastatic RCCs. Total RNA was extracted from formalin fixed paraffin embedded tissues and the expression of miR-21 was analyzed by real time PCR using TaqMan miR-21-specific probes. Results were normalized using RNU44 as an endogenous control. miRNA expression was analyzed in correlation with other clinicopathological parameters including tumor grade, stage, and progression-free survival.
Results: The expression of miR-21 was significantly increased in primary RCC when compared to normal kidney tissue. There was also differential expression between RCC subtypes and between RCC and oncocytoma. The highest levels of expression were found in clear cell and papillary RCC when compared to chromophobe RCC and oncocytoma. Also, there were significant differences of miR-21 expression among different stages of RCC with higher miR-21 expression being associated with later stage. There was an increase in miR-21 expression in metastatic RCC when compared to primary tumors. This, however, did not reach statistical significance. Survival analysis by Kaplan Meier showed patients with positive miR-21 tumors were more likely to have a recurrence than patients with tumors negative for miR-21 expression.
Conclusions: There is increased expression of miR-21 in kidney cancer which suggests it may play a role in the pathogenesis of RCC. Its level of expression can be used as a diagnostic marker, to distinguish between RCC tumor subtypes, and also as a prognostic marker in RCC. miR-21 can also be a therapeutic target for RCC.
Category: Genitourinary (including renal tumors)
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 103, Wednesday Morning