PRSS22 as a novel prognostic and immune regulatory biomarker in PanCancer multiomics analysis

Serine proteases are key mediators of tumorigenesis; however, the pan-cancer significance of PRSS22 remains poorly defined. This study comprehensively analyzes the multi-omics landscape and clinical relevance of PRSS22 across 33 cancer types using data from TCGA, HPA, and cBioPortal. We performed systematic analyses, including expression profiling (cancer vs. normal), prognosis (overall survival), characterization of the immune microenvironment, functional enrichment, and assessment of genomic alterations. PRSS22 expression demonstrated significant cancer-type specificity, with frequent overexpression observed in 10 cancer types and downregulation in 4 cancer types (p < 0.05). Notably, elevated tumor expression levels of PRSS22 were independently associated with worse overall survival in multiple cancers, specifically KIRC, LIHC, LUAD, and SKCM (p < 0.05). Despite showing downregulation at the mRNA level in KIRC, LIHC, and SKCM cancer cell lines as validated by qPCR, higher tumor tissue PRSS22 expression in patient cohorts of these cancers remained strongly associated with poor prognosis-a paradox suggesting potential non-cell-autonomous roles. Furthermore, PRSS22 levels showed associations with the tumor immune microenvironment. Functional enrichment analyses indicated that PRSS22 co-expressed/related genes are enriched in diverse biological processes relevant to cancer. Our pan-cancer analysis establishes PRSS22 as a multifaceted biomarker with prognostic value and links to tumor immunity, highlighting its complex, context-dependent roles across malignancies. These findings provide a crucial foundation for elucidating PRSS22's mechanisms and assessing its potential for diagnostic/prognostic applications.