Chang Xian, Lv Yang-Fan, He Jing, Cao Ya, Li Chang-Qing, Guo Qiao-Nan
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, People's Republic of China.
Department of Pathology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, People's Republic of China.
J Hepatocell Carcinoma. 2021 Mar 12;8:85-101. doi: 10.2147/JHC.S296438. eCollection 2021.
N6-methyladenosine (m6A) RNA methylation is the most prevalent modification of mammalian RNA, and it is associated with tumorigenesis and cancer progression. Its regulation is mediated via m6A-related regulators, including "erasers," "readers," and "writers". The present study evaluated the expression profile, risk signature and prognostic value of 13 m6A regulators in hepatocellular carcinoma (HCC) using different datasets, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and clinical samples.
We used 374 HCC samples derived from the TCGA database, 569 HCC samples from 2 GEO datasets, and clinical tumour and nontumour tissues derived from 60 patients with HCC who underwent surgery in Xinqiao Hospital Chongqing to assess the gene expression profiles and prognostic values of m6A-related regulators in HCC.
Eight of 13 core m6A-related regulators were overexpressed in all databases, including TCGA, GSE, clinical tumour and nontumour tissues of HCC. Two clusters (Cluster 1 and Cluster 2) were identified via consensus clustering. Cluster 2 was associated with poorer prognosis, higher tumour grade, higher AFP levels, and worse outcome compared to Cluster 1, which indicates that these m6A-related regulators are highly correlated with HCC malignancy. We performed survival analyses using the Log rank tests and a Cox regression model. Gene enrichment analysis was used to detect the related KEGG and GO pathways. We derived a prognostic risk signature using five selected m6A-related regulators.
Our work suggested that m6A-related regulators might be key participants in the tumour progression of HCC and potential biomarkers with prognostic value.
N6-甲基腺苷（m6A）RNA甲基化是哺乳动物RNA中最普遍的修饰，与肿瘤发生和癌症进展相关。其调控是通过m6A相关调节因子介导的，包括“去甲基化酶”“阅读蛋白”和“甲基转移酶”。本研究使用不同数据集，包括癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和临床样本，评估了13种m6A调节因子在肝细胞癌（HCC）中的表达谱、风险特征和预后价值。
我们使用了来自TCGA数据库的374例HCC样本、来自2个GEO数据集的569例HCC样本，以及来自重庆新桥医院60例行手术治疗的HCC患者的临床肿瘤和非肿瘤组织，以评估m6A相关调节因子在HCC中的基因表达谱和预后价值。
13个核心m6A相关调节因子中的8个在所有数据库中均高表达，包括TCGA、GSE以及HCC的临床肿瘤和非肿瘤组织。通过一致性聚类识别出两个聚类（聚类1和聚类2）。与聚类1相比，聚类2与更差的预后、更高的肿瘤分级、更高的甲胎蛋白水平和更差的结局相关，这表明这些m6A相关调节因子与HCC恶性程度高度相关。我们使用对数秩检验和Cox回归模型进行生存分析。基因富集分析用于检测相关的KEGG和GO通路。我们使用5个选定的m6A相关调节因子得出了一个预后风险特征。
我们的研究表明，m6A相关调节因子可能是HCC肿瘤进展的关键参与者和具有预后价值的潜在生物标志物。
