Genome-Scale Metabolic Model Analysis of Metabolic Differences between Lauren Diffuse and Intestinal Subtypes in Gastric Cancer

Abstract

Gastric cancer (GC) is one of the most lethal cancers worldwide; it has a high mortality rate, particularly in East Asia. Recently, genetic events (e.g., mutations and copy number alterations) and molecular signaling associated with histologically different GC subtypes (diffuse and intestinal) have been elucidated. However, metabolic differences among the histological GC subtypes have not been studied systematically. In this study, we utilized transcriptome-based genome-scale metabolic models (GEMs) to identify differential metabolic pathways between Lauren diffuse and intestinal subtypes. We found that diverse metabolic pathways, including cholesterol homeostasis, xenobiotic metabolism, fatty acid metabolism, the MTORC1 pathway, and glycolysis, were dysregulated between the diffuse and intestinal subtypes. Our study provides an overview of the metabolic differences between the two subtypes, possibly leading to an understanding of metabolism in GC heterogeneity.