M(5)C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in lung adenocarcinoma.
M(5)C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in lung adenocarcinoma.
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DOI：
10.21037/tlcr-21-351
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发表时间：
2021-05
影响因子：
4
通讯作者：
Zhu HC
中科院分区：
文献类型：
--
作者：
Chen H;Ge XL;Zhang ZY;Liu M;Wu RY;Zhang XF;Xu LP;Cheng HY;Sun XC;Zhu HC
近年来，免疫治疗取得了长足进展，表观遗传学的调控作用得到验证。然而，5-甲基胞嘧啶（m5C）在肿瘤微环境（TME）和免疫治疗反应中的作用仍不清楚。基于 11 个 m5C 调节因子，我们评估了 572 名肺腺癌 (LUAD) 患者的 m5C 修饰模式。 m5C 评分通过主成分分析 (PCA) 算法构建，以量化个体 LUAD 患者的 m5C 修饰模式。根据 11 个 m5C 调节因子鉴定出两种 m5C 甲基化修饰模式。这两种模式具有明显不同的 TME 免疫细胞浸润特征。接下来，筛选了226个与m5C表型相关的差异表达基因（DEG）。根据这些基因将患者分为三种不同的基因簇亚型，它们具有不同的TME免疫细胞浸润和预后特征。 m5C 评分的构建是为了量化各个 LUAD 患者的 m5C 修饰模式。我们发现m5C评分高组的预后较好。 m5C评分在预测预后中的作用也在数据集GSE31210中得到了验证。我们的研究表明，m5C 修饰在 LUAD 的 TME 调控中发挥着重要作用。 m5C调控模式的研究可能会对未来的肿瘤免疫治疗产生一些影响。
In recent years, immunotherapy has made great progress, and the regulatory role of epigenetics has been verified. However, the role of 5-methylcytosine (m5C) in the tumor microenvironment (TME) and immunotherapy response remains unclear. Based on 11 m5C regulators, we evaluated the m5C modification patterns of 572 lung adenocarcinoma (LUAD) patients. The m5C score was constructed by principal component analysis (PCA) algorithms in order to quantify the m5C modification pattern of individual LUAD patients. Two m5C methylation modification patterns were identified according to 11 m5C regulators. The two patterns had a remarkably distinct TME immune cell infiltration characterization. Next, 226 differentially expressed genes (DEGs) related to the m5C phenotype were screened. Patients were divided into three different gene cluster subtypes based on these genes, which had different TME immune cell infiltration and prognosis characteristics. The m5C score was constructed to quantify the m5C modification pattern of individual LUAD patients. We found that the high m5C score group had a better prognosis. The role of the m5C score in predicting prognosis was also verified in the dataset GSE31210. Our study revealed that m5C modification played a significant role in TME regulation of LUAD. Investigation of the m5C regulation mode may have some implications for tumor immunotherapy in the future.
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