Effect of BRCA2, BRAF, APC, and PTEN expression on the prognostic significance of surgical margin status in primary gastric adenocarcinoma.

455 Background: Gastric cancer is the fifth most common malignancy and the fourth leading cause of cancer-related mortality worldwide. Surgical resection with negative margins (R0) remains the cornerstone of curative therapy, yet the prognostic significance of residual disease (R1, R2) may be modified by tumor biology. BRCA2, BRAF, APC, and PTEN are key regulators of DNA repair, cell cycle progression, and tumor suppression, but their interaction with surgical margin outcomes in gastric adenocarcinoma has not been fully defined. Methods: The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) dataset was analyzed for clinical outcomes and RNA-Seq STAR counts for BRCA2, BRAF, APC, and PTEN. Expression was stratified into quartiles, with Q1–2 defined as low expression group (LEG) and Q3–4 as high expression group (HEG). Kaplan–Meier survival analysis was performed across R0, R1, and R2 resections, and survival differences tested by log-rank. Univariate and multivariate Cox proportional hazards models were used to identify predictors, adjusting for race, gender, and AJCC pathologic stage. Results: High expression of all four genes was associated with significantly worse survival in R2 resections. In BRCA2 HEG, R2 predicted poor survival (HR 11.2, 95% CI 5.65–22.1, p