Prognostic value of gene mutations in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.

[BACKGROUND] This meta-analysis aimed to evaluate the association between distinct mutations and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients.

[METHODS] A comprehensive literature search was conducted across major databases to identify studies reporting hazard ratios (HRs) and 95% confidence intervals (CIs) for OS associated with key mutations (G12D, G12R, and G12V) in PDAC patients, from inception until January 2025. Subgroup analyses were carried out based on disease stage (resectable and borderline resectable as early-stage disease and locally advanced and metastatic as late-stage disease) and treatment approaches (operation, chemotherapy, or combination of both).

[RESULTS] KRAS G12D mutation was significantly associated with poor OS (HR = 1.64, 95% CI: 1.28-1.99,  < 0.05). In subgroup analysis, G12D mutation was significantly associated with poor OS in those receiving chemotherapy (HR = 1.29, 95%CI: 1.18-1.39,  < 0.05) and in those with late-stage disease (HR = 1.29, 95%CI: 1.18-1.39,  < 0.05). G12R was significantly associated with improved OS in patients receiving chemotherapy (HR = 0.74, 95% CI: 0.56-0.99,  = 0.042). G12V had a significant association with improved OS in patients with early-stage disease (HR = 0.67, 95% CI: 0.52-0.86,  = 0.002).

[CONCLUSIONS] The study highlights the heterogeneous prognostic impact of mutations in PDAC. These findings suggest that the prognostic relevance of mutations in PDAC may depend on clinical factors such as treatment modality and disease stage.