Wang Wei, Sun Bo, Xia Yang, Sun Shenghong, He Chiyi
Department of Gastroenterology, Yijishan Hospital, Wannan Medical College, Wuhu, China.
Front Genet. 2020 Apr 23;11:306. doi: 10.3389/fgene.2020.00306. eCollection 2020.
Liver cancer (LC) is the fourth leading cause of cancer-related deaths worldwide. There is an urgent need to identify novel and reliable prognostic biomarkers for LC in order to improve patient outcomes. N6-methyladenosine (m6A) is the most common internal modification in eukaryotic mRNA and has been associated with various cancers, although its roles in the prognosis of LC remains to be elucidated. We analyzed the expression profiles of 15 m6A-related genes in the International Cancer Genome Consortium (ICGC) LIRI-JP dataset, and applied consensus clustering to stratify LC patients into two subgroups (Cluster 1 and Cluster 2). Cluster1 was significantly correlated to lower tumor stage and longer overall survival (OS). Gene set enrichment analysis showed that tumorigenic markers, including DNA repair, E2F targets, G2M checkpoint, and MYC targets V1, were enriched in Cluster2. We then constructed a prognostic risk model using three m6A-related genes that were identified as independent factors affecting OS. The nomogram based on the risk model score indicated good performance in predicting the 1-, 2- and 3-year survival of the LC patients. In conclusion, m6A-related genes are potential prognostic markers and therapeutic targets for LC.
肝癌（LC）是全球癌症相关死亡的第四大主要原因。迫切需要为肝癌识别新的可靠预后生物标志物，以改善患者预后。N6-甲基腺苷（m6A）是真核生物mRNA中最常见的内部修饰，并且已与多种癌症相关，尽管其在肝癌预后中的作用仍有待阐明。我们分析了国际癌症基因组联盟（ICGC）LIRI-JP数据集中15个m6A相关基因的表达谱，并应用一致性聚类将肝癌患者分为两个亚组（亚组1和亚组2）。亚组1与较低的肿瘤分期和较长的总生存期（OS）显著相关。基因集富集分析表明，包括DNA修复、E2F靶点、G2M检查点和MYC靶点V1在内的致瘤标志物在亚组2中富集。然后，我们使用三个被确定为影响总生存期的独立因素的m6A相关基因构建了一个预后风险模型。基于风险模型评分的列线图在预测肝癌患者1年、2年和3年生存率方面表现良好。总之，m6A相关基因是肝癌潜在的预后标志物和治疗靶点。
