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Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas
Authors:Jonas Busch  Bernhard Ralla  Monika Jung  Zofia Wotschofsky  Elena Trujillo-Arribas  Philipp Schwabe  Ergin Kilic  Annika Fendler  Klaus Jung
Abstract:

Background

Piwi-interacting RNAs (piRNAs) are small RNAs of 27–30 nucleotides mapping to transposons or clustering in repeat genomic regions. Preliminary studies suggest an important role in cancerogenesis. This study is the first one investigating their prognostic impact in clear cell renal cell cancer (ccRCC) patients.

Methods

Three piRNAs (piR-30924, piR-57125, and piR-38756) selected on the basis of initial piRNA microarray analyses were determined using RT-qPCR in non-metastatic (n = 76) and metastatic (n = 30) ccRCC tissue at the time of nephrectomy in comparison to normal renal tissue (n = 77) and tissue from distant ccRCC metastases (n = 13). Primary clinical end points were recurrence-free and overall survival.

Results

piR-57125 showed lower expression in metastatic than in non-metastatic tumors, whereas the expression of piR-30924 and piR-38756 increased in metastatic tumors. The higher expression of piR-30924 and piR-38756 as well as the lower expression of piR-57125 in metastatic primary tumors were significantly associated with tumor recurrence and overall survival. Multivariate Cox regression analyses revealed both piR-30924 and piR-57125 as independent prognostic predictors. This impact was even more pronounced in non-metastatic patients.

Conclusions

This study demonstrates that the expression levels of these piRNAs in primary non-metastatic and metastatic ccRCC tissue can serve as potential prognostic biomarkers in combination with clinicopathological factors.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-015-0180-3) contains supplementary material, which is available to authorized users.
Keywords:Clear cell renal cell carcinoma   piRNA   Prognosis   Metastasis   Recurrence   Overall survival
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