The Association of Death Receptors and TGF-β1 Expression in Urothelial Bladder Cancer and Their Prognostic Significance

TL;DR

This study explores how death receptors and TGF-β1 are linked to bladder cancer progression and patient survival, offering potential new insights for treatment.

Contribution

The study identifies distinct expression patterns of death receptors and TGF-β1 in bladder cancer and their independent prognostic significance.

Findings

High DR4 and FAS expression correlates with better survival in bladder cancer patients.

TGF-β1 high expression is an independent predictor of poor prognosis in urothelial bladder cancer.

Loss of death receptors is associated with muscle-invasive tumors, while non-invasive tumors retain receptor expression.

Abstract

Death receptor signalization that triggers the extrinsic apoptotic pathway and TGF-β1 have important roles in urothelial carcinogenesis, with a complex interplay between them. The aim of this research was to assess the association of death receptors DR4, DR5, and FAS as well as TGF-β1 immunohistochemical expression with the clinicopathological characteristics of urothelial bladder cancer (UBC) and to evaluate their prognostic significance. The decrease or loss of death receptors’ expression was significantly associated with muscle-invasive tumors, while non-invasive UBC often retains the expression of death receptors, which are mutually strongly linked. High DR4 expression is a marker of low-grade tumors and UBC associated with exposition to known carcinogens. Conversely, TGF-β1 was significantly associated with high tumor grade and advanced stage. High expression of DR4 and FAS indicates longer overall survival. High TGF-β1 signifies an inferior outcome and is an independent predictor of adverse prognosis in UBC patients. This study reveals the expression profile of death receptors in UBC and their possible interconnection with TGF-β1 and indicates independent prognostic significance of high FAS and TGF-β1 expression in UBC, which may contribute to deciphering the enigma of UBC heterogeneity in light of the rapid development of novel and effective therapeutic approaches, including targeting of the TRAIL-induced apoptotic pathway.

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