Abstract 1258: MMP23B expression and protein levels in blood and urine are associated with bladder cancer risk

Urothelial bladder cancer (UBC) represents a public health problem because of its elevated incidence and relapse rate. After prostate cancer, UBC is the most frequent malignancy of the urinary tract with a higher incidence in men and smokers. To date, there are no suitable biomarkers for an early diagnosis or detection of relapse/progression. In the attempt to improve diagnostic accuracy and to overcome the disadvantages of current diagnostic strategies, biomarkers found in easily accessible biofluids, such as blood or urine, represent a non-invasive and promising approach. The first aim of this study was the identification of reliable biomarkers of UBC risk starting with whole gene expression profile in white blood cells from 66 UBC cases and 70 controls. We observed a lower expression of MMP23B and its relative pseudogene MMP23A in UBC compared to controls (LogFC=-0.37, FDR adjusted p-value=0.02 and LogFC=-0.23, FDR adjusted p-value=0.03, respectively, adjusted for age, smoking, and batch). Thus, we investigated MMP23B protein levels both in plasma (49 controls and 53 UBC) and in urine (57 controls and 59 UBC) samples, to confirm gene expression observations. Unexpectedly, both western blot evidences and ELISA quantification showed increased MMP23B levels in UBC cases respect to controls, reaching a statistical significance in urine (mean UBC=1797.70pg/ml, mean controls=1075.73pg/ml, p-value=0.02). A positive trend of association of MMP23 levels was observed also for grade and risk. As the lack of correlation between mRNA and protein levels could be due to a post-transcriptional crosstalk mediated by microRNAs (miRNAs), we investigated the expression levels of miRNAs targeting MMP23B gene in urine of UBC patients and controls. We identified 5 differentially expressed miRNAs targeting MMP23B 3'UTR in UBC cases and controls. The present outcomes indicate a potential role of MMP23B as non-invasive UBC biomarkers. Moreover, we reported the first evidence of MMP23B secretion both in plasma and urine, suggesting a role of this poorly characterized metalloproteinase in UBC. Further analyses are needed to better elucidate the mechanism of regulation of MMP23B expression by miRNAs present in UBC urine. Citation Format: Barbara Pardini, Alessandra Allione, Clara Viberti, Giuliana Giribaldi, Stefano Turini, Cornelia Di Gaetano, Simonetta Guarrera, Francesca Cordero, Marco Oderda, Marco Allasia, Paolo Gontero, Carlotta Sacerdote, Alessio Naccarati, Paolo Vineis, Giuseppe Matullo. MMP23B expression and protein levels in blood and urine are associated with bladder cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1258.