二代测序技术检测胃癌患者基因突变及其临床病理特征分析OA

Objective To analyze the gene mutation profile of Chinese patients with gastric cancer and to explore its correlations with clinicopathological characteristics and prognosis.Methods Fifty-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).Results Somatic 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.Conclusion Chinese 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.