Cohort-based pan-cancer analysis and experimental studies reveal ISG15 gene as a novel biomarker for prognosis and immunotherapy efficacy prediction.

ABSTRACT: ISG15, an interferon-stimulated ubiquitin-like protein, plays a multifaceted role in tumorigenesis and immune regulation. This study comprehensively evaluates ISG15 as a prognostic biomarker and predictor of immunotherapy response through pan-cancer bioinformatics analysis and experimental validation. By integrating multiomics data from TCGA, GEO, and clinical cohorts, we found that ISG15 is significantly overexpressed in multiple cancers and generally correlates with poor prognosis. Elevated ISG15 expression is associated with increased immune checkpoint gene expression, particularly PD-L1, and immune infiltration, notably M2-like tumor-associated macrophages. Immunohistochemistry and multiplexed immunofluorescence confirmed a strong positive correlation between ISG15, PD-L1, and M2-TAM i

SUBMITTER: Wei J 

PROVIDER: S-EPMC11985735 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature