Single-cell N6-methyladenosine-related genes function within the tumor microenvironment to affect the prognosis and treatment sensitivity in patients with gastric cancer

Background Gastric cancer (GC) ranks fifth for morbidity and third for mortality worldwide. The N-6-methyladenosine (m(6)A) mRNA methylation is crucial in cancer biology and progression. However, the relationship between m(6)A methylation and gastric tumor microenvironment (TME) remains to be elucidated. Methods We combined single-cell and bulk transcriptome analyses to explore the roles of m(6)A-related genes (MRG) in gastric TME. Results Nine TME cell subtypes were identified from 23 samples. Fibroblasts were further grouped into four subclusters according to different cell markers. M(6)A-mediated fibroblasts may guide extensive intracellular communications in the gastric TME. The m(6)A-related genes score (MRGs) was output based on six differentially expressed single-cell m(6)A-related genes (SCMRDEGs), including GHRL, COL4A1, CAV1, GJA1, TIMP1, and IGFBP3. The protein expression level was assessed by immunohistochemistry. We identified the prognostic value of MRGs and constructed a nomogram model to predict GC patients' overall survival. MRGs may affect treatment sensitivity in GC patients. Conclusion Our study visualized the cellular heterogeneity of TME at the single-cell level, revealed the association between m(6)A mRNA modification and intracellular communication, clarified MRGs as an independent risk factor of prognosis, and provided a reference for follow-up treatment.