食管癌是一种恶性程度很高的疾病，预后较差。尽管食管癌的研究最近取得了进展，但治疗和预后的改善有限。 N6-甲基腺苷 (m6A) 是一种 RNA 修饰，已被广泛研究并参与许多生物学行为，包括肿瘤发生和进展。因此，对 m6A 修饰的更多研究可能会增加我们对食管癌发病机制的了解并提供潜在的靶点。在我们的研究中，我们整合了来自癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据库的食管癌公共数据。使用无监督聚类分析将患者分为不同组。基因集变异分析（GSVA）以非参数和无监督模式进行。我们通过单样本基因集富集分析（ssGSEA）评估了免疫细胞浸润。使用经验贝叶斯方法鉴定 m6A 簇之间的差异表达基因 (DEG)。多变量和单变量Cox回归模型均用于预后分析。我们概述了食管癌中 23 个 m6A 调节因子的基因变异和表达及其对生存的影响。根据 m6A 调节因子的总体表达水平，将患者分为三个 m6A 簇 (A-C)，具有不同的免疫细胞浸润丰度、基因表达特征和预后。在m6A簇中，我们鉴定了206个DEG，根据这些DEG将患者分为4个基因簇（A-D）。根据那些对生存有显着影响的 DEG 计算每位患者的定量 m6A 评分。除 2 型辅助性 T (Th2) 细胞外，所有类型免疫细胞的浸润与 m6A 评分呈负相关。 M6Acluster C 表现出最低的 m6A 评分、最丰富的免疫细胞浸润和最差的预后，表明免疫排除表型。一致的是，m6A 得分最低的基因簇 D 显示出最差的预后。简而言之，食管癌患者表现出不同的 m6A 修饰模式。定量评分表明，m6A评分最低的患者表现出最丰富的免疫细胞浸润和最差的预后。该 m6A 评分系统有望评估 m6A 修饰模式、表征免疫浸润并指导个性化治疗和预后预测。© 2023。作者。

Esophageal cancer is a highly malignant disease with poor prognosis. Despite recent advances in the study of esophageal cancer, there has been only limited improvement in the treatment and prognosis. N6-methyladenosine (m6A), a type of RNA modification, has been extensively investigated and is involved in many biological behaviors, including tumorigenesis and progression. Thus, more research on m6A modification may increase our understanding of esophageal cancer pathogenesis and provide potential targets. In our study, we integrated the public data of esophageal cancer from The Cancer Genome Atlas (TCGA) and Gene-Expression Omnibus (GEO) databases. Unsupervised clustering analysis was used to classify patients into different groups. Gene set variation analysis (GSVA) was performed in a nonparametric and unsupervised mode. We evaluated immune cell infiltration by single sample gene set enrichment analysis (ssGSEA). Differentially expressed genes (DEGs) among m6A clusters were identified using Empirical Bayesian approach. Both multivariate and univariate Cox regression models were used for prognostic analysis. We provided an overview of gene variation and expression of 23 m6A regulators in esophageal cancer, as well as their effects on survival. Based on the overall expression level of m6A regulators, patients were classified into three m6A clusters (A-C) with different immune cell infiltration abundance, gene expression signatures and prognosis. Among m6A clusters, we identified 206 DEGs, according to which patients were classified into 4 gene clusters (A-D). Quantitative m6A score was calculated for each patient based on those DEGs with significant impact on survival. The infiltration of all types of immune cells except type 2 T helper (Th2) cells were negatively correlated with m6A score. M6Acluster C exhibited the lowest m6A score, the most abundant immune cell infiltration, and the worst prognosis, suggesting an immune excluded phenotype. Consistently, gene cluster D with the lowest m6A score showed the worst prognosis. In short, patients with esophageal cancer showed different m6A modification patterns. Quantitative scoring indicated that patients with the lowest m6A score exhibited the most abundant immune cell infiltration and the poorest prognosis. This m6A scoring system is promising to assess m6A modification pattern, characterize immune infiltration and guide personalized treatment and prognostic prediction.© 2023. The Author(s).