Next-Generation Sequencing-Based Detection of Gene Mutations and Its Association With Clinicopathological Features in Gastric Cancer

ObjectiveTo analyze the gene mutation profile of Chinese patients with gastric cancer and to explore its correlations with clinicopathological characteristics and prognosis.MethodsFifty-five patients with gastric cancer were enrolled. Next-generation sequencing was performed to detect mutations in cancer-related genes, microsatellite instability, and tumor mutational burden. The associations of high-frequency mutated genes with clinicopathological features and progression-free survival (PFS) were analyzed. Key findings were validated and ethnic heterogeneity was assessed using The Cancer Genome Atlas stomach adenocarcinoma cohort (n = 436). ResultsSomatic mutations were identified in 85.45% (47/55) of patients. The most frequently mutated genes were TP53 (29.09%), ARID1A (16.36%), CDH1 (14.55%), LRP1B (14.55%), and PIK3CA (12.73%). TP53 mutations were associated with T4 stage (P = 0.028) and diffuse-type gastric cancer (P = 0.008). CDH1 mutations were enriched in signet-ring cell carcinoma (P = 0.012) and poorly differentiated tumors (P = 0.006). Pathogenic germline mutations were identified in 20% (11/55) of patients. Univariate survival analysis revealed that CDH1 mutation was an independent poor prognostic factor for PFS (hazard ratio = 3.110, 95% confidence interval: 3.370-20.000). Validation in The Cancer Genome Atlas cohort confirmed that the poor prognostic effect of CDH1 mutation was present only in the Asian subgroup (hazard ratio = 5.00, 95% confidence interval: 2.01-12.43), demonstrating significant ethnic heterogeneity.ConclusionChinese patients with gastric cancer exhibit a distinct gene mutation profile, and key gene mutations are closely associated with tumor aggressiveness. This multi-cohort validation study indicates ethnic differences in the prognostic value of genes such as CDH1, highlighting the importance of precision molecular classification in the Chinese population.