Occurrence of differing metabolic dysregulations, a glucose driven and another fatty acid centric in gastric cancer subtypes.

ABSTRACT

Gastric cancer is one of the most common cancers and ranks third in cancer-related deaths across globe. Cancer cells are known to take advantage of the altered metabolic processes to sustain their survival, proliferation, and cancer progression. In this investigation, we explored the available genome-wide expression profiles of few hundreds of gastric tumors and non-cancerous gastric tissues and analyzed in the context of metabolic pathways. Gastric tumors were investigated for the metabolic processes related to glucose metabolism, glucose transport, glutamine metabolism, and fatty acid metabolism, by metabolic pathway-focused gene set enrichment analysis. Notably, all glucose metabolism and glutamine metabolism-related gene sets were found enriched in intestinal subtype gastric tumors. On the other hand, the gene sets related to glucose transport and glucan (glycan) metabolisms are enriched in diffuse subtype gastric tumors. Strikingly, fatty acid metabolisms, fatty acid transport, and fat differentiation-related signatures are also highly activated in diffuse subtype gastric tumors. Exploration of the recently established metabolome profile of the massive panel of cell lines also revealed the metabolites of glucose and fatty acid metabolic pathways to show the differing abundance across gastric cancer subtypes. The subtype-specific metabolic rewiring and the existence of two distinct metabolic dysregulations involving glucose and fatty acid metabolism in gastric cancer subtypes have been identified. The identified differing metabolic dysregulations would pave way for the development of targeted therapeutic strategies for the gastric cancer subtypes.