Bioinformatics analysis and in vitro studies identify COX7C as a prognostic predictor in gastric adenocarcinoma

Stomach adenocarcinoma (STAD) remains a significant threat to human health. This study sought to discover clinically relevant biomarkers for STAD by integrating bioinformatics analysis and in vitro experimental methods.

We utilized the GSE64951 dataset to screen for differentially expressed genes (DEGs), which were then subjected to weighted gene co-expression network analysis (WGCNA). Candidate modules were subjected to Molecular Complex Detection (MCODE) analysis to extract key genes. Survival analysis and immune infiltration analysis were conducted to identify hub genes associated with STAD prognosis. Among them, cytochrome c oxidase subunit 7 C (COX7C) was selected for further investigation. Its expression levels in normal versus tumor tissues were compared, and its diagnostic performance was assessed via receiver operating characteristic (ROC) curve analysis. Functional experiments, including COX7C overexpression and knockdown, were performed in MGC803 cells to evaluate its effects on viability, apoptosis, migration, and invasion.

WGCNA identified multiple gene modules, among which the blue and turquoise modules showed the strongest correlations with clinical traits and were selected for further analysis. MCODE analysis identified 11 key genes. COX7C was identified as hub gene, and its prognostic signature demonstrated robust predictive power. Gene Set Enrichment Analysis (GSEA) indicated that COX7C was significantly involved in pathways such as amino acid metabolism and non - alcoholic fatty liver disease. Notably, COX7C mRNA expression was significantly downregulated in STAD tissues (AUC = 0.7253, P = 0.0032). Functional experiments demonstrated that overexpression of COX7C significantly inhibited cell viability, promoted apoptosis, and reduced cell migration and invasion. Conversely, knockdown of COX7C led to opposite effects.

COX7C functions as a tumor suppressor and a potential prognostic biomarker in STAD. These findings provide new insights into STAD pathogenesis and suggest COX7C as a promising target for improving diagnostic and therapeutic strategies.