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

单细胞 N6-甲基腺苷相关基因在肿瘤微环境中发挥作用,影响胃癌患者的预后和治疗敏感性

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作者:Zehua Wang #, Chen Chen #, Jiao Shu, Jiaoyu Ai, Yihan Liu, Haoyue Cao, Yongxu Jia, Yanru Qin

Background

Gastric cancer (GC) ranks fifth for morbidity and third for mortality worldwide. The N6-methyladenosine (m6A) mRNA methylation is crucial in cancer biology and progression. However, the relationship between m6A methylation and gastric tumor microenvironment (TME) remains to be elucidated.

Conclusion

Our study visualized the cellular heterogeneity of TME at the single-cell level, revealed the association between m6A mRNA modification and intracellular communication, clarified MRGs as an independent risk factor of prognosis, and provided a reference for follow-up treatment.

Methods

We combined single-cell and bulk transcriptome analyses to explore the roles of m6A-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. M6A-mediated fibroblasts may guide extensive intracellular communications in the gastric TME. The m6A-related genes score (MRGs) was output based on six differentially expressed single-cell m6A-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.

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