M7G methylated core genes (METTL1 and WDR4) and associated RNA risk signatures are associated with prognosis and immune escape in HCC

Abstract

AbstractN7 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.