COG8 serves as a predictive and prognostic biomarker in lung adenocarcinoma and other human malignancies

Abstract

The main objective of this study is to investigate the dysregulated expression, clinical relevance, and underlying mechanisms of COG8 in lung adenocarcinoma (LUAD) and other human malignancies. We assembled multi-cohort microarray and RNA sequencing data for tumor and non-tumor controls from global repositories including ArrayExpress, Gene Expression Omnibus, The Cancer Genome Atlas, and Genotype-Tissue Expression. COG8 protein expression in LUAD was evaluated using immunohistochemical staining. Differential expression was assessed using standardized mean difference (SMD) for pooled effects and Wilcoxon rank-sum tests for individual datasets. Clinical relevance of COG8 was examined using receiver operating characteristic analyses and Cox/Kaplan–Meier survival analyses. Correlation between COG8 expression and tumor mutation burden, microsatellite instability, neoantigen count, and TIMER scores was evaluated using Spearman’s rank correlation. Gene set enrichment analysis was conducted to explore the potential signaling pathways associated with COG8 across tumor types. COG8 mRNA was higher in LUAD compared to the control group (SMD = 0.29, 95% CI: 0.12–0.46, p < 0.05), consistent with COG8 protein levels by immunohistochemistry (p < 0.05). Elevated mRNA expression was associated with longer overall survival in LUAD (p < 0.05) and showed moderate discrimination between LUAD and controls (AUC = 0.72). COG8 mRNA was also overexpressed in 11 additional cancer types (p < 0.05). Higher COG8 expression was linked to worse prognosis in seven cancers (HR > 1; p < 0.05) and to improved overall and/or disease-specific survival in four cancers (HR < 1; p < 0.05). In certain cancers, COG8 expression correlated with tumor mutation burden, microsatellite instability, neoantigen count, and immune infiltration levels (p < 0.05). COG8 may impact signaling pathways such as cytokine-cytokine receptor interaction. COG8 exhibits aberrant expression in LUAD and eleven other human malignancies, holding clinical significance as a predictive and prognostic biomarker.