Correlation between High PD-L1 and EMT/Invasive Genes Expression and Reduced Recurrence-Free Survival in Blood-Circulating Tumor Cells from Patients with Non-Muscle-Invasive Bladder Cancer
Maria Beatrice Morelli, Consuelo Amantini, J.A. Rossi De Vermandois, Marilena Gubbiotti, Antonella Giannantoni, Ettore Mearini, Federica Maggi, Massimo Nabissi, Oliviero Marinelli, Matteo Santoni, Alessia Cimadamore, Rodolfo Montironi, Giorgio Santoni
Abstract
Background: PD-L1 represents a crucial immune checkpoint molecule in the tumor microenvironment, identified as a key target for cancer immunotherapy. A correlation between PD-L1 and EMT-related genes expression in various human cancers has been suggested. Methods: By ScreenCell filtration, digital droplet PCR and confocal microscopy analysis, we aimed to investigate the expression of PD-L1 and EMT/invasive genes (TWIST1, ZEB1, VIMENTIN, TIMP2) in circulating tumor cells (CTCs) collected from the blood of non-muscle-invasive bladder cancer (NMIBC) patients, assessing the prognostic value of these biomarkers in the disease. Welchs’ test and Mann–Whitney U test, correlation index, Kaplan–Meier, Univariate and Multivariate Cox hazard proportional analysis were used. Results: Higher PD-L1, TIMP2 and VIM mRNA levels were found in pT1 compared to pTa NMIBC. As evaluated by Kaplan–Meier and Univariate and Multivariate Cox analysis, enhancement of PD-L1, TWIST1 and TIMP2 expression reduces the recurrent free survival in NMIBC patients. Conclusions: High PD-L1, TWIST1 and TIMP2 mRNAs mark the recurrent-NMIBC patients and by reducing the RFS represent negative prognostic biomarkers in these patients.