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Expression pattern and prognostic value of N6-methyladenosine RNA methylation key regulators in hepatocellular carcinoma
Mutagenesis ( IF 2.7 ) Pub Date : 2021-09-01 , DOI: 10.1093/mutage/geab032
Min Deng 1, 2, 3 , Lin Fang 4 , Shao-Hua Li 1, 2, 3 , Rong-Ce Zhao 1, 2, 3 , Jie Mei 1, 2, 3 , Jing-Wen Zou 1, 2, 3 , Wei Wei 1, 2, 3 , Rong-Ping Guo 1, 2, 3
Affiliation  

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.

中文翻译:

N6-甲基腺苷RNA甲基化关键调控因子在肝细胞癌中的表达模式及预后价值

肝细胞癌(HCC)仍然是全球最常见的恶性肿瘤之一。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 甲基化调节因子的预测价值并建立 HCC 的预后模型。本研究从癌症基因组图谱(TCGA)数据库中获取HCC的数据,检测15个基因的表达水平和生存情况。然后我们确定了具有不同临床因素的两个HCC集群,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。五个基因产生的风险评分将HCC患者分为高风险组和低风险组。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来准确预测 HCC 患者的预后。HCC 样本中 13 个 m6A RNA 甲基化调节因子的表达水平显着上调。簇 1 和簇 3 的预后较差。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,并开发了基于m6A RNA甲基化调节因子的预测模型,可以准确预测HCC患者的预后,为临床治疗提供有意义的指导。
更新日期:2021-09-01
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