Comprehensive pan-cancer analysis of HSPA1B as a biomarker for prognosis and immunity

HSPA1B, a member of the HSP70 family, functions as a molecular chaperone essential for protein folding and stress responses. Emerging evidence indicates that HSPA1B is overexpressed in multiple cancers and contributes to tumor progression and immune modulation. However, its comprehensive role across cancer types remains unclear. To determine whether HSPA1B could serve as a universal biomarker, we performed an integrative pan-cancer analysis to investigate its expression, regulation, and function. Results demonstrate that HSPA1B is significantly upregulated across multiple cancers and strongly associated with poor prognosis. Genomic analyses reveal that gene amplification is the predominant driver of its overexpression, which is further linked to increased genomic instability. Epigenetic regulation contributes to HSPA1B expression, as evidenced by its inverse correlation with DNA methylation levels. Notably, HSPA1B expression is positively associated with cancer-associated fibroblast infiltration and negatively with CD8⁺ T cell abundance, indicating its role in establishing an immunosuppressive tumor microenvironment. We further selected cholangiocarcinoma (CHOL) as a model due to its high HSPA1B expression and limited treatment options, and found that HSPA1B contributes to chemotherapy resistance and malignant phenotypes. Collectively, this study identifies HSPA1B as a pan-cancer oncogenic driver and positions it as a promising predictive biomarker and therapeutic target.