Cancer Cell International (Jan 2024)

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

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

DOI
https://doi.org/10.1186/s12935-024-03227-2
Journal volume & issue
Vol. 24, no. 1
pp. 1 – 13

Abstract

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Abstract 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. 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. 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.

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