β2-Microglobulin is a potential pan-cancer biomarker and immunotherapy target

Background : A important component of MHC-I-mediated antigen presentation, β2-Microglobulin (B2M), has a rising importance in carcinogenesis and immunological control. Although implicated in many malignancies, its pan-cancer prognostic value and therapeutic prospects are unknown. Methods : Multiple-omics analysis was performed on TCGA, CPTAC, and GEO datasets. Tools included TIMER2 (immune infiltration), GEPIA2 (survival/pathological staging), cBioPortal (genomic changes), UALCAN (methylation), and STRING (protein interactions). Drug sensitivity correlations were evaluated using GSCALite and CTRP. Key Results Expression characteristics: B2M is highly expressed in CHOL, GBM, and KIRC, while it is lowly expressed in COAD and LUAD (P<0.001). Prognostic value: High B2M expression is significantly associated with poor prognosis in LGG and UVM (OS: P<0.001), but is associated with better survival in KIRC (P=0.043). Genetic variation: B2M has the highest mutation frequency (>20%) in DLBC, mainly consisting of L15Ffs * 41 truncated mutations. Immune regulation: B2M expression is positively correlated with CD8+T cell and Tregs infiltration, and significantly correlated with TMB and MSI . Functional pathway: B2M regulates tumor immunity through JAK-STAT and NOD like receptor signaling pathways, and its interacting genes (HLA-A/B/C, etc.) are significantly enriched in MHC-I complex function (P<0.05). Conclusion : As a pan cancer biomarker, the expression level of B2M is closely related to prognosis, immune microenvironment and treatment response, and may become a new target of immunotherapy. This study provides a theoretical basis for the individualized treatment of cancer, but further experiments are needed to verify its mechanism.