Clinical and Genetic Characteristics of Early and Advanced Gastric Cancer

Abstract

Gastric cancer (GC) persists as the fourth most prevalent cause of global cancer-related mortality, presenting a challenge due to the scarcity of available therapeutic strategies. Precision medicine is crucial not only in the treatment but also in the management of GC. We performed gene panel sequencing with Oncomine focus assay comprising 52 cancer-associated genes and MSI analysis in 100 case-matched gastric cancer cases. A comprehensive analysis of clinical and genetic characteristics was conducted on these genetic results and clinicopathological findings. Upon comparison of clinicopathological characteristics, significant differences between early gastric cancer (EGC) and advanced gastric cancer (AGC) were observed in tumor location (p = 0.003), Lauren classification (p = 0.015), T stage (p = 0.000), and N stage (p = 0.015). The six most frequently mutated genes were PIK3CA (29%, 10/35), ERBB2 (17%, 6/35), KRAS (14%, 5/35), ALK (6%, 2/35), ESR1 (6%, 2/35), and FGFR3 (6%, 2/35). Regarding genetic variation, there was a tendency for the N stage to be higher in GC patients with mutated genes (p = 0.014). The frequency of mutations in GC patients was statistically significantly higher in AGC (n = 24) compared to EGC (n = 11) (odds ratio, 2.792; 95% confidence interval, 1.113 to 7.007; p = 0.026). Six of the ten GC patients carrying mutated genes and exhibiting MSI were classified into intestinal-type and undifferentiated GC, with the location of the tumor being in the lower-third. Among these patients, five harbored mutated PIK3CA, while the remaining patient had a mutation in ALK. Conclusions: AGC patients more frequently exhibited alterations of PIK3CA, KRAS, and ERBB2 as somatic oncogenic drivers, and displayed a higher prevalence of cumulative genetic events, including increased rates of PIK3CA mutations, enhanced detection of immunotherapy biomarkers, and mutations of the ESR1 gene.