Abstract
BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy with a poor prognosis and limited effective prognostic markers or therapeutic strategies. This study aims to construct and validate a prognostic risk model based on oxidative stress-related genes (OSRGs) to stratify patient risk and guide individualized treatment for CCA. METHODS: Using data from 66 tumors and 36 control samples obtained from the TCGA and GEO databases, we identified 3,632 differentially expressed genes (DEGs). Intersection with oxidative stress-related genes revealed 122 OSRGs, from which 10 key prognostic genes were selected through univariate Cox and LASSO regression analyses. Model performance was assessed with Kaplan-Meier survival, ROC curve, PCA, and t-SNE analyses. Tumor microenvironment (TME) features, immune cell infiltration, and chemosensitivity to cisplatin and 5-fluorouracil were also evaluated. RESULTS: The 10-gene model, including genes like RORA and GRIN2A, effectively distinguished between high- and low-risk groups, with high RORA and GRIN2A expression correlating with improved survival. High-risk groups displayed increased immune and ESTIMATE scores, with significant differences in immune cell infiltration. Chemosensitivity analysis indicated differential responses to various chemotherapeutics in high-risk patients. CONCLUSION: This OSRG-based model demonstrates strong prognostic potential, stratifying CCA patients by risk and survival outcomes. The model provides insights into personalized treatment strategies, potentially advancing therapeutic interventions for CCA.