Expression of m6A Regulators Correlated With Immune Microenvironment Predicts Therapeutic Efficacy and Prognosis in Gliomas.
Expression of m6A Regulators Correlated With Immune Microenvironment Predicts Therapeutic Efficacy and Prognosis in Gliomas.
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与免疫微环境相关的 m6A 调节因子的表达可预测胶质瘤的治疗效果和预后
DOI：
10.3389/fcell.2020.594112
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发表时间：
2020
影响因子：
5.5
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Xu S;Tang L;Dai G;Luo C;Liu Z
背景N6-甲基腺苷（m6 A）RNA甲基化和肿瘤免疫微环境在肿瘤发生发展中起着重要作用。然而，它们在胶质瘤中的相关性仍有待充分阐明。方法从CGGA、TCGA和伦勃朗数据库中提取2144例脑胶质瘤患者，其中325例为训练队列，1819例为验证队列。通过Kaplan-Meier分析评价组间生存差异。通过共识聚类将患者分成亚组。应用ESTIMATE算法计算免疫和基质评分。采用TIMER算法对免疫细胞的浸润进行表征。通过多变量考克斯回归分析构建风险特征。结果19种m6 A调节因子在脑胶质瘤组织中高表达。m6 A调节因子的表达与胶质瘤的病理类型、分级、异柠檬酸脱氢酶（IDH）状态和1 p19 q状态有关。通过一致聚类确定了两个亚组，其中聚类1与良好的预后、高基质和免疫评分以及高免疫浸润相关。当根据患者的风险评分将其分为高风险组和低风险组时，我们发现高风险组的患者的预后较差。此外，高危组患者的间质和免疫评分较高，免疫浸润丰度较高。这些结果在包含三个独立数据集的验证队列中得到进一步验证。低危组未行放化疗或单纯化疗者生存率较低。结论m6 A调节因子与胶质瘤的免疫微环境有关，可预测胶质瘤的预后和疗效。
Background N6-methyladenosine (m6A) RNA methylation and tumor immune microenvironment played crucial roles in cancer development. However, their association in gliomas remains to be fully elucidated. Methods A total of 2144 glioma patients from CGGA, TCGA, and Rembrandt databases were extracted in our study, in which 325 were set as the training cohort and 1819 were defined as the validation cohort. Survival differences evaluated by Kaplan–Meier analysis between groups. Patients were clustered into subgroups by consensus clustering. ESTIMATE algorithm was applied to calculate immune and stroma scores. The infiltration of immune cells was characterized by TIMER algorithm. The risk signature was constructed by multivariate Cox regression analysis. Results Nineteen m6A regulators were highly expressed in glioma tissues. The expression of m6A regulators was associated with prognoses, grade, isocitrate dehydrogenase (IDH) status, and 1p19q status of gliomas. Two subgroups were identified by consensus clustering, in which cluster 1 was associated with favorable prognosis, high stroma and immune scores, and high immune infiltration. When the patients were divided into high risk and low risk groups based on their risk scores, we found that patients in the high risk group had poor prognoses. Besides, patients in the high risk group had a higher stroma and immune scores, and higher abundance of immune infiltration. These results were further verified in the validation cohort, which contained three independent datasets. Moreover, patients in the low risk group enjoyed better prognoses without chemoradiotherapy or single chemotherapy. Conclusion Our study revealed that m6A regulators could predict the prognosis and therapeutic efficacy, and were also associated with the immune microenvironment in gliomas.