Comprehensive pan-cancer analysis reveals CGB5 is a potential promising predictive and immunotherapeutic biomarker.

Background: Existing studies substantiate the notion that CGB5 plays a pivotal role in various cancers, including gastric and ovarian cancers, and is strongly associated with patient prognosis. However, to date, there have been no comprehensive reports investigating the role of CGB5 in pan-cancer analysis. Methods: In this study, an in-depth investigation of CGB5 in pan-cancer was conducted through multiple public databases, including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), UALCAN, cBioPortal Platform, Gene Set Cancer Analysis (GSCA), Kaplan-Meier Plotter, TIMER, TISIDB, SangerBox Website, and Metascape database. The genomic, transcriptomic, epigenetic, immune microenvironmental, and clinical prognostic significance of CGB5 across various cancers was systematically analyzed. Furthermore, CGB5 expression in gastric cancer cells was experimentally detected, and the potential mechanisms underlying its impact on prognosis were elucidated. Results: This study shows that CGB5 exhibits diverse expression patterns in most tumors, including high, low, or no significant expression changes. Compared to normal tissues, CGB5 is significantly up-regulated in six tumor types, such as liver, lung, and gastric cancers. Its expression correlates positively with tumor stroma content and immune grading but negatively with immunological markers. Additionally, CGB5 is associated with specific immune sub-types in various cancers, including endometrial, testicular germ cell, and gastric adenocarcinoma, and closely linked to clinical features of gastric cancer patients. CGB5 primarily involves immune-related pathways, such as "Primary immunodeficiency," "CD8 TCR signaling pathway," and "PD-1 checkpoint signaling." Conclusion: This study demonstrates that CGB5 expression is closely associated with immune cell infiltration across cancer types, showing significant variation in infiltration patterns among tumor types. CGB5 is significantly up-regulated in various malignancies and strongly correlates with cancer patient prognoses, specifically in malignancies like GC and PAAD. Overall, these findings indicate CGB5 as a promising biomarker for pan-cancer diagnosis and prognosis.