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Sunitinib has greatly improved the survival of clear cell renal cell carcinoma (ccRCC) patients in recent years. However, 20–30% of treated patients do not respond. To identify miRNAs and genes associated with a response, comparisons were made between biopsies from responder and non-responder ccRCC patients. Using integrated transcriptomic analyses, we identified 37 miRNAs and 60 respective target genes, which were significantly associated with the NF-kappa B, PI3K-Akt and MAPK pathways. We validated expression of the miRNAs (<i>miR-223</i>, <i>miR-155</i>, <i>miR-200b</i>, <i>miR-130b</i>) and target genes (<i>FLT1</i>, <i>PRDM1</i> and <i>SAV1</i>) in 35 ccRCC patients. High levels of <i>miR-223</i> and low levels of <i>FLT1</i>, <i>SAV1</i> and <i>PRDM1</i> were associated with worse overall survival (OS), and combined <i>miR-223</i> + <i>SAV1</i> levels distinguished responders from non-responders (AUC = 0.92). Using immunohistochemical staining of 170 ccRCC patients, VEGFR1 (<i>FLT1</i>) expression was associated with treatment response, histological grade and RECIST (Response Evaluation Criteria in Solid Tumors) score, whereas SAV1 and BLIMP1 (<i>PRDM1</i>) were associated with metachronous metastatic disease. Using in situ hybridisation (ISH) to detect <i>miR-155</i> we observed higher tumoural cell expression in non-responders, and non-tumoural cell expression with increased histological grade. In summary, our preliminary analysis using integrated miRNA-target gene analyses identified several novel biomarkers in ccRCC patients that surely warrant further investigation.