Mitofusin-2 Down-Regulation Predicts Progression of Non-Muscle Invasive Bladder Cancer

Abstract: Identification of markers predicting disease outcome is a major clinical issue for nonmuscleinvasive bladder cancer (NMIBC). The present study aimed to determine the role of themitochondrial proteins Mitofusin-2 (Mfn2) and caseinolytic protease P (ClpP) in predicting theoutcome of NMIBC. The study population consisted of patients scheduled for transurethral resectionof bladder tumor upon the clinical diagnosis of bladder cancer (BC). Samples of the main bladdertumor and healthy-looking bladder wall from patients classified as NMIBC were tested for Mfn2 andClpP. The expression levels of these proteins were correlated to disease recurrence, progression. Mfn2and ClpP expression levels were significantly higher in lesional than in non-lesional tissue. Low-riskNMIBC had significantly higher Mfn2 expression levels and significantly lower ClpP expressionlevels than high-risk NMIBC; there were no differences in non-lesional levels of the two proteins.Lesional Mfn2 expression levels were significantly lower in patients who progressed whereas ClpPlevels had no impact on any survival outcome. Multivariable analysis adjusting for the EORTCscores showed that Mfn2 downregulation was significantly associated with disease progression.In conclusion, Mfn2 and ClpP proteins were found to be overexpressed in BC as compared tonon-lesional bladder tissue and Mfn2 expression predicted disease progression.