Abstract
BACKGROUND: The survival outcomes of younger patients with gastric cancer (GC) have remained controversial. This study explores the clinicopathological characteristics, survival outcomes, and genetic alterations of younger and older patients with GC. METHODS: Patients with GC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1998-2018. Survival analysis was conducted using Kaplan-Meier estimates and Cox proportional hazards models. Sequencing datasets were enrolled from The Cancer Genome Atlas (TCGA) and Memorial Sloan-Kettering Cancer Center (MSKCC) databases. RESULTS: A total of 1146 younger (<40 years of age) and 16,988 older (≥40 years of age) cases were included in the study. Younger patients had more poorly differentiated lesions than older patients (53.7% vs. 33.8%, respectively; p < 0.0001), and were more often pTNM stage IV (19.5% vs. 11.8%, respectively; p < 0.001). The 5-year overall survival (OS) of patients from the NCCGCDB increased from 1998 to 2018. Younger patients with pTNM stage III had a lower survival rate than older patients (p = 0.014), while no differences by age were observed at other stages. The mutation frequency of the LRP1B, GNAS, APC, and KMT2D genes was higher for older than younger patients (p < 0.05 for all genes). While not significantly different, younger patients from the TCGA and MSKCC databases were more likely to have CDH1, RHOA, and CTNNB1 gene mutations. CONCLUSIONS: A stable proportion and improved survival of younger patients were reported using NCCGCDB data. Younger patients with pTNM stage III had lower rates of survival than older patients. Distinct molecular characteristics were identified in younger GC patients which may partly explain the histopathology and prognosis specific to this subpopulation.