The Matrisome Is Associated with Metabolic Reprograming in Stem-like Phenotypes of Gastric Cancer

SIMPLE SUMMARY: Our results suggested a correlation between the metabolic reprogramming associated with the high-matrisome group and stem-like phenotype in gastric cancer. Carbohydrate sulfotransferase 7 was found to be associated with the signaling transduction of overexpressed oncogenes and tumor suppressor genes in the high-matrisome group. The high expression of glycosaminoglycan biosynthesis-chondroitin sulfate metabolic pathway genes was associated with poor prognosis. ABSTRACT: The extracellular matrix (ECM) is an important regulator of all cellular functions, and the matrisome represents a major component of the tumor microenvironment. The matrisome is an essential component comprising genes encoding ECM glycoproteins, collagens, and proteoglycans; however, its role in cancer progression and the development of stem-like molecular subtypes in gastric cancer is unknown. We analyzed gastric cancer data from five molecular subtypes (n = 497) and found that metabolic reprograming differs based on the state of the matrisome. Approximately 95% of stem-like cancer type samples of gastric cancer were in the high-matrisome category, and energy metabolism was considerably increased in the high-matrisome group. Particularly, high glycosaminoglycan biosynthesis-chondroitin sulfate metabolic reprograming was associated with an unfavorable prognosis. Glycosaminoglycan biosynthesis-chondroitin sulfate metabolic reprograming may occur according to the matrisome status and contribute to the development of stem-like phenotypes. Our analysis suggests the possibility of precision medicine for anticancer therapies.