Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
State Key Laboratory of Oncology in South China, Guangzhou, China.
Mutagenesis. 2021 Oct 6;36(5):369-379. doi: 10.1093/mutage/geab032.
Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins' interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients' prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients' prognosis and provide meaningful guidance for clinical treatment.
肝细胞癌(HCC)仍然是全球最常见的恶性肿瘤之一。用于预测 HCC 预后和治疗效果的生物标志物的准确性并不理想。N6-甲基腺苷(m6A)甲基化调节剂在各种肿瘤中起着至关重要的作用。我们的研究旨在进一步确定 m6A 甲基化调节剂的预测价值,并为 HCC 建立一个预后模型。在这项研究中,我们从癌症基因组图谱(TCGA)数据库中获得了 HCC 的数据,并检查了 15 个基因的表达水平和生存率。然后,我们确定了具有不同临床因素的两种 HCC 聚类,构建了预后标志物并分析了基因集富集、蛋白质相互作用和基因共表达。根据 13 个基因的表达,通过共识聚类确定了三个亚组。由五个基因生成的风险评分将 HCC 患者分为高风险和低风险组。此外,我们开发了一种可以识别高危 HCC 的预后标志物。最后,开发了一种新的预后列线图,以准确预测 HCC 患者的预后。在 HCC 样本中,13 个 m6A RNA 甲基化调节剂的表达水平显著上调。簇 1 和簇 3 的预后更差。高危组患者预后不良。此外,风险评分是 HCC 患者的独立预后因素。总之,我们揭示了 m6A RNA 甲基化修饰在 HCC 中的关键作用,并基于 m6A RNA 甲基化调节剂开发了一个预测模型,该模型可以准确预测 HCC 患者的预后,并为临床治疗提供有意义的指导。