Jiangnan University Medical Center, WuXi, China.
Wuxi No.2 People's Hospital, WuXi, China.
BMC Med Genomics. 2023 Aug 1;16(1):179. doi: 10.1186/s12920-023-01614-8.
N7 methylguanosine (m7G) has a crucial role the development of hepatocellular carcinoma (HCC). This study aimed to investigate the impact of the m7G methylation core genes (METTL1 and WDR4) and associated RNA risk signatures on HCC. we found m7G methylation core genes (METTL1 and WDR4) were upregulated in four HCC cell lines, and downregulation of METTL1 and WDR4 attenuated HCC cell proliferation, migration, and invasion. Moreover, METTL1 and WDR4 are upregulated in HCC tissues, and that there is a significant positive correlation between them. METTL1 and WDR4 were identified as independent prognostic markers for HCC by employing overall survival (OS), disease-specific survival (DSS), Progression Free Interval survival (PFI), and univariate/multivariate Cox analyses. We identified 1479 coding RNAs (mRNAs) and 232 long non-coding RNAs (lncRNAs) associated with METTL1 / WDR4 by using weighted coexpression network analysis (WGCNA) and co-clustering analysis. The least absolute shrinkage and selection operator (lasso) were used to constructing mRNA and lncRNA risk signatures associated with the METTL1 / WDR4. These risk were independent poor prognostic factors in HCC. Furthermore, we found that METTL1 / WDR4 expression and mRNA / lncRNA risk scores were closely associated with TP53 mutations. Clinicopathological features correlation results showed that METTL1 / WDR4 expression and mRNA / lncRNA risk score were associated with the stage and invasion depth (T) of HCC. To predict the overall survival of HCC individuals, we constructed a nomogram with METTL1/WDR4 expression, mRNA/lncRNA risk score, and clinicopathological features. In addition, we combined single-cell sequencing datasets and immune escape-related checkpoints to construct an immune escape-related protein-protein interaction(PPI) network. In conclusion, M7G methylated core genes (METTL1 and WDR4) and associated RNA risk signatures are associated with prognosis and immune escape in HCC.
N7 甲基鸟苷（m7G）在肝细胞癌（HCC）的发展中起着关键作用。本研究旨在探讨 m7G 甲基化核心基因（METTL1 和 WDR4）和相关 RNA 风险特征对 HCC 的影响。我们发现，四种 HCC 细胞系中 m7G 甲基化核心基因（METTL1 和 WDR4）上调，METTL1 和 WDR4 的下调抑制 HCC 细胞的增殖、迁移和侵袭。此外，METTL1 和 WDR4 在 HCC 组织中上调，且它们之间呈显著正相关。通过总生存（OS）、疾病特异性生存（DSS）、无进展间隔生存（PFI）和单因素/多因素 Cox 分析，METTL1 和 WDR4 被确定为 HCC 的独立预后标志物。我们通过加权共表达网络分析（WGCNA）和共聚类分析，确定了与 METTL1/WDR4 相关的 1479 个编码 RNA（mRNA）和 232 个长非编码 RNA（lncRNA）。最小绝对收缩和选择算子（lasso）用于构建与 METTL1/WDR4 相关的 mRNA 和 lncRNA 风险特征。这些风险是 HCC 的独立不良预后因素。此外，我们发现 METTL1/WDR4 表达和 mRNA/lncRNA 风险评分与 TP53 突变密切相关。临床病理特征相关性结果表明，METTL1/WDR4 表达和 mRNA/lncRNA 风险评分与 HCC 的分期和浸润深度（T）有关。为了预测 HCC 患者的总体生存率，我们构建了一个包含 METTL1/WDR4 表达、mRNA/lncRNA 风险评分和临床病理特征的列线图。此外，我们结合单细胞测序数据集和免疫逃逸相关检查点构建了一个免疫逃逸相关蛋白-蛋白相互作用（PPI）网络。总之，M7G 甲基化核心基因（METTL1 和 WDR4）和相关 RNA 风险特征与 HCC 的预后和免疫逃逸有关。
