Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma.

MicroRNAs (miRNAs) play an important role as regulators of gene expression in tumourigenesis by controlling many biological processes in growth, development, differentiation and apoptosis. Previous studies have shown an altered expression of specific miRNAs in clear cell renal cell carcinoma (ccRCC). But the function in cancerogenesis and metastasis in this tumour type is almost unknown. We aimed at identifying specific miRNA expression patterns that are associated with metastasis and prognosis in ccRCC patients. MiRNA of 30 human ccRCC including ten non-metastatic tumours, four tumours with metastasis after 3 years or later and four tumours with primary metastasis was isolated. We analysed the miRNA expression by using microarrays and qRT-PCR. We detected a miRNA signature that distinguishes between metastatic and non-metastatic ccRCC, including miR-451, miR-221, miR-30a, miR-10b and miR-29a. Furthermore, we identified a group of 12 miRNAs, such as let-7 family, miR-30c, miR-26a, which are decreased in highly aggressive primary metastatic tumours. We found also correlations between expression levels of specific miRNAs with progression-free survival and overall survival. Our findings suggest that specific miRNAs are involved in metastasis and have an impact on the progression of the ccRCC. Furthermore, we identified specific miRNAs characterising very aggressive tumours with early metastasis. In addition, we determined candidate markers associated with survival of the patients. Thus, it seems possible to use miRNAs for prediction of progression to distant metastasis and prognosis analysing the primary tumour.