Work

Molecular stratification of prostate cancer through sensory perception-related multi-omics analysis reveals chemoresistant mechanisms

Year: 2025

Type: article

Abstract: BACKGROUND: Advanced prostate cancer (PCa) displays significant genetic heterogeneity and therapy resistance, yet the role of sensory perception pathways in its progression remains unclear. METHODS: We performed an integrative multi-omics analysis of sensory perception-linked mRNAs and lncRNAs from TCGA and scRNA-seq data. Unsupervised consensus clustering defined three molecular subtypes (CS1-CS3). Key biomarkers were validated in patient tissues and serum. Immune and stromal infiltration were quantified using TIDE and ESTIMATE. Single-cell trajectories characterized TSC22D3-positive T cells, and NicheNet mapped ligand-receptor interactions. RESULTS: Three subtypes emerged, with CS1 showing the poorest prognosis, marked chemotherapy resistance, and pronounced stromal-immune crosstalk. CS1 tumors exhibited elevated B- and T-cell infiltration and increased oxidative phosphorylation in TSC22D3-positive T cells. NicheNet analysis identified the TNF-CCL20 axis as a central mediator of immunosuppressive signaling and chemoresistance in CS1. CONCLUSIONS: This study establishes sensory perception-associated molecular subtypes in PCa and links CS1 chemoresistance to immune microenvironment reprogramming via TNF-CCL20 signaling. These findings offer mechanistic insights into PCa progression and suggest actionable targets to overcome therapeutic resistance.

Source: Cellular Oncology

DOI: 10.1007/s13402-025-01099-w

Authors: Shi Li, Ye Tian, Yu Sun, Tian Xu, Wei Wang

Institutions: Dalian University of Technology, Shanghai Jiao Tong University

Language: English

Topic: Prostate Cancer Treatment and Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,390