A pan-cancer analysis of CTSC as a candidate prognostic and immune-related biomarker

Cathepsin C (CTSC) is a lysosomal protease involved in immune regulation and inflammatory responses, with emerging roles in tumor progression and microenvironment remodeling. Although CTSC dysregulation has been observed in several cancers, its pan-cancer significance, immune-related functions, and clinical relevance remain poorly characterized.

We conducted an integrated multi-omics analysis using data from TCGA, GTEx, CPTAC, cBioPortal, HPA, and other public databases. We evaluated CTSC expression patterns, prognostic value, immune infiltration, epigenetic regulation, mutation profiles, and drug sensitivity across diverse cancer types. Analytical methods included survival analysis, functional enrichment, immune correlation assays, and single-cell sequencing.

CTSC was widely expressed and significantly dysregulated in multiple cancers. High CTSC expression correlated with poor prognosis in 10 cancer types and was linked to advanced tumor stage. CTSC expression was associated with immune checkpoint genes, infiltration of cancer-associated fibroblasts (CAFs), and γδ T cells, indicating a dual role in both promoting and suppressing anti-tumor immunity. Additionally, CTSC expression correlated with DNA hypermethylation, RNA methylation regulators, TMB, and MSI. Drug sensitivity analysis suggested that high CTSC expression may enhance response to certain anti-cancer agents.

Our study underscores the multifaceted role of CTSC in tumor immunity and progression, supporting its potential as a prognostic biomarker and therapeutic target across cancer types. These findings provide a foundation for further mechanistic and clinical investigation into CTSC-targeted strategies.