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

被引:2
作者
Wang, Zehua [1 ]
Chen, Chen [1 ]
Shu, Jiao [2 ]
Ai, Jiaoyu [3 ]
Liu, Yihan [1 ]
Cao, Haoyue [1 ]
Jia, Yongxu [1 ]
Qin, Yanru [1 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Oncol, Zhengzhou 450052, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Pathol, Zhengzhou 450052, Peoples R China
[3] Nanchang Univ, Affiliated Hosp 1, Nanchang 330006, Peoples R China
基金
中国国家自然科学基金;
关键词
Gastric cancer; Single-cell analysis; m(6)A; Tumor microenvironment; Prognosis; FIBROBLASTS;
D O I
10.1186/s12935-024-03227-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:13
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