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

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.