Mutational Separation and Clinical Outcomes of and in Gastric Cancer

Background: Gastric cancer (GC) is a deadly tumor with the fifth highest occurrence and highest global mortality rates. Owing to its heterogeneity, the underlying mechanism of GC remains unclear, and chemotherapy offers little benefit to individuals.

Aim: To investigate the clinical outcomes of and mutations in GC.

Methods: In this study, 202 gastric adenocarcinoma tumor tissues and their corresponding normal tissues were collected. A total of 490 genes were identified using target capture. Through -test and Wilcoxon rank-sum test, somatic mutations, microsatellite instability, and clinical statistics, including overall survival, were detected, compared, and calculated.

Results: The mutation rates of 32 genes, including , , , and exceeded 10%. mutations had a slightly lower overall occurrence rate (33%). The mutation rate was significantly higher in advanced stages (stage III/IV) than that in early stages (stage I/II) ( < 0.05). In contrast, mutations were significantly associated with diffuse GC. is related to poor prognosis of advanced-stage tumors; nevertheless, CDH1 corresponds to a diffuse type of cancer. is exclusively mutated in and is primarily affected by two distinct GC mechanisms.

Conclusion: Different somatic mutation patterns in and indicate two major mechanisms of GC.