Novel Therapeutic Targets and Biomarkers Associated with Bladder Cancer-Associated Fibroblasts (CAFs) Promoted by Bisphenol A

Abstract

The escalating incidence of health issues linked to environmental pollutants, specifically endocrine-disrupting chemicals (EDCs), has emerged as a dire consequence of modern industrialization. Bisphenol A (BPA), a widespread EDC, is under scrutiny for its potential role in exacerbating bladder cancer via the modulation of cancer-associated fibroblasts (CAFs). CAFs are integral to the tumor microenvironment, influencing cancer progression through their interactions with immune cells and secretion of various factors and exosomes. By recognizing the critical role of CAFs, this study delves into their utility as therapeutic targets, focusing on the identification of reliable biomarkers within CAFs for bladder cancer. Through weighted correlation network analysis, genes associated with T cell activity were pinpointed, culminating in the creation of a CAFs-based, immune-related gene prognostic model. Central to this model is ANPEP, an enzyme whose expression level not only serves as an indicator of T cell infiltration but also implicates a substantial role in the CAF-mediated immunotherapy responses for bladder cancer. Our investigation posits ANPEP as a linchpin in regulating CAF functions, offering a novel perspective wherein targeting ANPEP may reduce the adverse side effects commonly associated with traditional immunotherapies. Furthermore, ANPEP-targeted strategies could lessen the tumor mutational burden in bladder cancer patients. Empirical evidence from our proliferation and invasion assays indicates that heightened ANPEP expression is correlated with diminished patient survival. These insights pave the way for tailored immunotherapeutic approaches in bladder cancer treatment, emphasizing the modulation of CAFs by ANPEP.