MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma.
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Authors
Trevisani, F
Ghidini, M
Larcher, A
Lampis, A
Lote, H
Manunta, P
Alibrandi, MTS
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
Braconi, C
Fassan, M
Hahne, JC
Montorsi, F
Valeri, N
Ghidini, M
Larcher, A
Lampis, A
Lote, H
Manunta, P
Alibrandi, MTS
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
Braconi, C
Fassan, M
Hahne, JC
Montorsi, F
Valeri, N
Document Type
Journal Article
Date
2016-11-01
Date Accepted
2016-09-22
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.
Citation
British journal of cancer, 2016, 115 (11), pp. 1343 - 1350
Source Title
Publisher
SPRINGERNATURE
ISSN
0007-0920
eISSN
1532-1827
Collections
Research Team
Signal Transduction & Molecular Pharmacology
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics