癌症源于影响癌基因和抑癌基因的遗传和表观遗传异常，再加上基因突变。 N6-甲基腺苷 (m6A) RNA 修饰受甲基化调节因子的调节，与肿瘤增殖、分化、肿瘤发生、侵袭和转移有关。然而，m6A 修饰模式在胃癌 (GC) 肿瘤微环境中的作用仍知之甚少。在本研究中，我们利用 31 个 m6A 调节因子分析了 267 个 GC 样本中的 m6A 修饰模式。使用共识聚类，我们确定了 GC 的两个独特子组。 GC 患者被分为高浸润和低浸润队列，以评估五种具有预后意义的免疫细胞类型的浸润比例。利用GC中的差异基因，我们通过加权基因共表达网络分析确定了一个“绿色”模块。采用LASSO回归方法建立风险预测模型。“绿色”模块同时连接m6A RNA甲基化簇和免疫浸润模式。基于“模块成员资格”和“基因重要性”，识别出37个​​枢纽基因，并建立了包含9个枢纽基因的风险预测模型。此外，甲基化RNA免疫沉淀和RNA免疫沉淀分析表明，YTHDF1提高了DNMT3B的表达，从而协同促进GC的发生和发展。我们阐明了 YTHDF1 调节 DNMT3B 的分子机制，并探讨了 m6A 和 5mC 修饰之间的串扰。m6A RNA 甲基化调节因子在胃癌的恶性进展和肿瘤微环境浸润的动态中发挥着重要作用。评估 GC 患者的 m6A 修饰模式和肿瘤微环境浸润特征有望成为有价值的预后生物标志物。版权所有 © 2024 Huo、Zhang、Zhang、Wang、Hu、Ma、Wang、Yuan、Qin、Teng、Yu、Huang 和 Wang。

Cancers arise from genetic and epigenetic abnormalities that affect oncogenes and tumor suppressor genes, compounded by gene mutations. The N6-methyladenosine (m6A) RNA modification, regulated by methylation regulators, has been implicated in tumor proliferation, differentiation, tumorigenesis, invasion, and metastasis. However, the role of m6A modification patterns in the tumor microenvironment of gastric cancer (GC) remains poorly understood.In this study, we analyzed m6A modification patterns in 267 GC samples utilizing 31 m6A regulators. Using consensus clustering, we identified two unique subgroups of GC. Patients with GC were segregated into high- and low-infiltration cohorts to evaluate the infiltration proportions of the five prognostically significant immune cell types. Leveraging the differential genes in GC, we identified a "green" module via Weighted Gene Co-expression Network Analysis. A risk prediction model was established using the LASSO regression method.The "green" module was connected to both the m6A RNA methylation cluster and immune infiltration patterns. Based on "Module Membership" and "Gene Significance", 37 hub genes were identified, and a risk prediction model incorporating nine hub genes was established. Furthermore, methylated RNA immunoprecipitation and RNA Immunoprecipitation assays revealed that YTHDF1 elevated the expression of DNMT3B, which synergistically promoted the initiation and development of GC. We elucidated the molecular mechanism underlying the regulation of DNMT3B by YTHDF1 and explored the crosstalk between m6A and 5mC modification.m6A RNA methylation regulators are instrumental in malignant progression and the dynamics of tumor microenvironment infiltration of GC. Assessing m6A modification patterns and tumor microenvironment infiltration characteristics in patients with GC holds promise as a valuable prognostic biomarker.Copyright © 2024 Huo, Zhang, Zhang, Wang, Hu, Ma, Wang, Yuan, Qin, Teng, Yu, Huang and Wang.