Background

RNA methylation modifying plays an important role in the occurrence and progression of a range of human cancers including hepatocellular carcinoma (HCC), which is characterized by a mass of genetic and epigenetic alterations. However, the treatment targeting these alterations is limited.

Methods

We used comprehensive bioinformatics analysis to analyze the correlation between cancer-associated RNA methylation regulators and HCC malignant features in network datasets.

Results

We identified two HCC subgroups (cluster 1 and 2), which had clearly distinct clinicopathological, biofunctional and prognostic characteristics, by consensus clustering. The cluster 2 subgroup correlated with malignancy of the primary tumor, higher tumor stage, higher histopathological grade and higher frequency of TP53 mutation, as well as with shorter survival when compared with cluster 1. Gene enrichment indicated that the cluster 2 correlated to the tumor malignancy signaling and biological processes. Based on these findings, an 11-gene risk signature was built, which not only was an independent prognostic marker but also had an excellent power to predict the tumor features.

Conclusions

Our study indicated that RNA methylation regulators are vital for HCC malignant progression and provide an important evidence for RNA methylation, methylation regulators are actionable targets for anticancer drug discovery.

中文翻译：

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整合转录组和体细胞突变以鉴定作为肝细胞癌预后标志物的 RNA 甲基化调节因子

背景

RNA 甲基化修饰在包括肝细胞癌 (HCC) 在内的一系列人类癌症的发生和进展中起着重要作用，其特征是大量的遗传和表观遗传改变。然而，针对这些改变的治疗是有限的。

方法

我们使用综合生物信息学分析来分析网络数据集中癌症相关的 RNA 甲基化调节因子与 HCC 恶性特征之间的相关性。

结果

我们通过共识聚类确定了两个 HCC 亚组（集群 1 和 2），它们具有明显不同的临床病理学、生物功能和预后特征。与第 1 组相比，第 2 组亚组与原发肿瘤的恶性程度、更高的肿瘤分期、更高的组织病理学分级和更高的TP53突变频率以及更短的生存期相关。 基因富集表明第 2 组与肿瘤恶性相关信号和生物过程。基于这些发现，构建了一个 11 基因风险特征，它不仅是一个独立的预后标志物，而且具有极好的预测肿瘤特征的能力。

结论

我们的研究表明，RNA 甲基化调节因子对 HCC 恶性进展至关重要，并为 RNA 甲基化提供了重要证据，甲基化调节因子是抗癌药物发现的可操作靶点。