Twenty to 40% localised RCC patients may experience recurrence after curative surgery. Limited miRNA predictors have been identified for ccRCC recurrence.
Through a multi-phase study design, we analysed miRNAs in tissues obtained from 203 ccRCC patients. Paired t-test was used for tumour-normal comparisons and Cox regression model was performed to compute hazard ratios (HRs) and corresponding 95% CIs.
A 17-miRNA signature was identified that can concordantly classify >95% of tumour/adjacent normal samples. Significant enrichment was found as 6 out of 17 miRNAs were associated with obesity (binomial probability=0.001). Decreased levels of miR-204-5p and miR-139-5p were each associated with an approximately three-fold increased risk of recurrence (P<0.01). Risk score was generated based on expressions of miR-204-5p and miR-139-5p, and the trend test was significant in both discovery and validation sets (Pfor trend<0.05). Striking MST reduction was observed for patients with a high-risk score (high vs low: discovery, 9.4 vs >97.7 months; validation, 20.8 vs >70.3 months). Expressions of miR-204-5p were also associated with body mass index (β=5.64, P<0.001). Significant inverse correlations were observed and validated between miR-204-5p and 13 obesity-related genes (r<0, P<0.01).
We identified 17 miRNAs dysregulated in ccRCC tissues and showed that low expressions of miR-204-5p and miR-139-5p were associated with the higher risk of recurrence. The link between miR-204-5p and ccRCC recurrence may be partially mediated by regulating the expression of targeted obesity-related genes.British Journal of Cancer advance online publication 1 December 2016; doi:10.1038/bjc.2016.392 www.bjcancer.com.
British journal of cancer. 2016 Jan 01 [Epub ahead of print]
X Shu, M A Hildebrandt, J Gu, N M Tannir, S F Matin, J A Karam, C G Wood, X Wu
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.