MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma

Francesco Trevisani, Michele Ghidini, Alessandro Larcher, Andrea Lampis, Hazel Lote, Paolo Manunta, Maria Teresa Sciarrone Alibrandi, Laura Zagato, Lorena Citterio, Giacomo Dell'Antonio, Cristina Carenzi, Giovambattista Capasso, Massimo Rugge, Paolo Rigotti, Roberto Bertini, Luciano Cascione, Alberto Briganti, Andrea Salonia, Fabio Benigni, Chiara BraconiMatteo Fassan, Jens Claus Hahne, Francesco Montorsi, Nicola Valeri

Research output: Contribution to journalArticle

Abstract

Background:A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes.Methods:Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT-PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD.Results:The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy.Conclusions:miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN.

Original languageEnglish
Pages (from-to)1343-1350
Number of pages8
JournalBritish Journal of Cancer
Volume115
Issue number11
DOIs
Publication statusPublished - Nov 22 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Trevisani, F., Ghidini, M., Larcher, A., Lampis, A., Lote, H., Manunta, P., Alibrandi, M. T. S., Zagato, L., Citterio, L., Dell'Antonio, G., Carenzi, C., Capasso, G., Rugge, M., Rigotti, P., Bertini, R., Cascione, L., Briganti, A., Salonia, A., Benigni, F., ... Valeri, N. (2016). MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma. British Journal of Cancer, 115(11), 1343-1350. https://doi.org/10.1038/bjc.2016.329