Cai Zhiqiang, Zhang Jianbo, Liu Ziying, Su Jiahao, Xu Jing, Li Zhenjun, Meng Hongliang, Zhang Heng, Huang Minjie, Zhao Donghai, Duan Chuanzhi, He Xuying
Department of Cerebrovascular Surgery, Engineering Technology Research Centre of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Neurosurgery, Langzhong City People's Hospital, Langzhong, China.
Ann Transl Med. 2021 Aug;9(15):1241. doi: 10.21037/atm-21-3139.
N6-methyladenosine (m6A) RNA methylation regulators play crucial role in tumorigenicity and progression. However, their biological significance in primary glioblastomas (GBM) has not been fully elucidated.
In the present study, we evaluated the 22 m6A RNA regulators using the integrated data of primary GBM samples from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. The different m6A modification patterns and m6A-related gene signature in primary GBM were distinguished by using principal component analysis. Single-sample gene set enrichment analysis was introduced to assess the relative level of immune infiltration. Gene set variation analysis was performed to calculate the enrichment score of the signaling pathways for different clusters. An m6A scoring scheme was established to evaluate the m6A modification pattern in individual tumors in order to predict prognosis and evaluate tumor microenvironment (TME) cell infiltration, immune response, and chemotherapy effect in primary GBM.
Two distinct m6A modification subgroups associated with different clinical features and biological pathways were identified among the 371 primary GBM. Based on 132 prognostic m6A phenotype-related differentially expressed genes (DEGs) between 2 m6A cluster subgroups, an m6A scoring model was constructed to assess the m6A modification pattern in individual tumors. The high-m6A score group was associated with better prognosis and immune response and worse chemotherapy effect.
The findings of the present study indicate the potential role of m6A modification in primary GBM, which will help enhance our understanding of TME characteristics, predict clinical prognosis, and provide important insight into effective immunotherapy and chemotherapy.
N6-甲基腺苷（m6A）RNA甲基化调节因子在肿瘤发生和进展中起关键作用。然而，它们在原发性胶质母细胞瘤（GBM）中的生物学意义尚未完全阐明。
在本研究中，我们使用来自癌症基因组图谱（The Cancer Genome Atlas）和中国胶质瘤基因组图谱（Chinese Glioma Genome Atlas）数据库的原发性GBM样本的整合数据，评估了22种m6A RNA调节因子。通过主成分分析区分原发性GBM中不同的m6A修饰模式和m6A相关基因特征。引入单样本基因集富集分析来评估免疫浸润的相对水平。进行基因集变异分析以计算不同簇的信号通路富集分数。建立了一种m6A评分方案，以评估个体肿瘤中的m6A修饰模式，从而预测原发性GBM的预后并评估肿瘤微环境（TME）细胞浸润、免疫反应和化疗效果。
在371例原发性GBM中鉴定出两个与不同临床特征和生物学途径相关的不同m6A修饰亚组。基于两个m6A簇亚组之间的132个与预后m6A表型相关的差异表达基因（DEG），构建了一个m6A评分模型，以评估个体肿瘤中的m6A修饰模式。高m6A评分组与较好的预后和免疫反应相关，但化疗效果较差。
本研究结果表明m6A修饰在原发性GBM中的潜在作用，这将有助于增强我们对TME特征的理解，预测临床预后，并为有效的免疫治疗和化疗提供重要见解。
