MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma.
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.
Division of Molecular Pathology, The Institute of Cancer Research, London, UK.|Department of Urology, San Raffaele Scientific Institute, Milan, Italy.|Division of Oncology/Unit of Urology; IRCCS Ospedale San Raffaele, Milan, Italy.
Francesco
F
Trevisani
Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Michele
M
Ghidini
Department of Urology, San Raffaele Scientific Institute, Milan, Italy.|Division of Oncology/Unit of Urology; IRCCS Ospedale San Raffaele, Milan, Italy.
Alessandro
A
Larcher
Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Andrea
A
Lampis
Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Hazel
H
Lote
Division of Nephrology and Dialysis, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Genomics of Renal Disease and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Paolo
P
Manunta
Division of Nephrology and Dialysis, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Maria Teresa Sciarrone
MT
Alibrandi
Genomics of Renal Disease and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Laura
L
Zagato
Genomics of Renal Disease and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Lorena
L
Citterio
Department of Pathology, San Raffaele Scientific Institute, Milan, Italy.
Giacomo
G
Dell'Antonio
Department of Urology, San Raffaele Scientific Institute, Milan, Italy.|Division of Oncology/Unit of Urology; IRCCS Ospedale San Raffaele, Milan, Italy.
Cristina
C
Carenzi
Department of Nephrology, Second University of Naples, Naples, Italy.
Giovambattista
G
Capasso
Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
Massimo
M
Rugge
Department of Surgical, Oncological and Gastroenterological Sciences, Kidney and Pancreas Transplantation Unit, University of Padua, Padua, Italy.
Paolo
P
Rigotti
Department of Urology, San Raffaele Scientific Institute, Milan, Italy.|Division of Oncology/Unit of Urology; IRCCS Ospedale San Raffaele, Milan, Italy.
Roberto
R
Bertini
Bioinformatics Core Unit, Institute of Oncology Research, Bellinzona, Switzerland.
Luciano
L
Cascione
Department of Urology, San Raffaele Scientific Institute, Milan, Italy.|Division of Oncology/Unit of Urology; IRCCS Ospedale San Raffaele, Milan, Italy.
Alberto
A
Briganti
Department of Urology, San Raffaele Scientific Institute, Milan, Italy.|Division of Oncology/Unit of Urology; IRCCS Ospedale San Raffaele, Milan, Italy.
Andrea
A
Salonia
Department of Urology, San Raffaele Scientific Institute, Milan, Italy.|Division of Oncology/Unit of Urology; IRCCS Ospedale San Raffaele, Milan, Italy.
Fabio
F
Benigni
Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.|Department of Medicine, The Royal Marsden NHS Trust, London, UK.
Chiara
C
Braconi
Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
Matteo
M
Fassan
Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
Jens Claus
JC
Hahne
Department of Urology, San Raffaele Scientific Institute, Milan, Italy.|Division of Oncology/Unit of Urology; IRCCS Ospedale San Raffaele, Milan, Italy.
Francesco
F
Montorsi
Division of Molecular Pathology, The Institute of Cancer Research, London, UK.|Department of Medicine, The Royal Marsden NHS Trust, London, UK.
Nicola
N
Valeri
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D005919:Glomerular Filtration Rate; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D035683:MicroRNAs / Q000378:metabolism*; D009392:Nephrectomy / Q000379:methods*
D014408:Biomarkers, Tumor; C546818:MIRN193 microRNA, human; D035683:MicroRNAs