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; Jacopo Adolfo Rossi de Vermandois; Marilena Gubbiotti; Antonella Giannantoni; Ettore Mearini; Federica Maggi; Massimo Nabissi; Oliviero Marinelli; Matteo Santoni; Alessia Cimadamore; Rodolfo Montironi; Giorgio Santoni

doi:10.3390/cancers13235989

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

Cancers (Basel). 2021 Nov 28;13(23):5989. doi: 10.3390/cancers13235989.

Authors

Affiliations

¹ School of Pharmacy, Section of Experimental Medicine, University of Camerino, 62032 Camerino, Italy.
² School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.
³ Urologic and Andrologic Clinics, University of Perugia, 05100 Perugia, Italy.
⁴ Department of Urology, San Donato Hospital, 52100 Arezzo, Italy.
⁵ Department of Medical and Surgical Sciences, University of Siena, 53100 Siena, Italy.
⁶ Neurosciences, Functional and Surgical Urology Unit, Santa Maria alle Scotte Hospital, 53100 Siena, Italy.
⁷ Department of Molecular Medicine, University Sapienza, 00185 Rome, Italy.
⁸ Oncology Unit, Macerata Hospital, 62100 Macerata, Italy.
⁹ Section of Pathological Anatomy, Department of Biomedical Sciences and Public Health School of Medicine, Polytechnic University of Marche Region, Umberto I Hospitals, 60121 Ancona, Italy.
¹⁰ Molecular Medicine and Cell Therapy Foundation, Department of Clinical and Molecular Sciences, Polytechnic University of Marche Region, 60126 Ancona, Italy.

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.

Keywords: CTC; EMT; NMIBC; PD-L1; RFS; TIMP2; TWIST1; immunotherapy.

Abstract

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