Multi-omics analysis and validation of the tumor microenvironment of hepatocellular carcinoma under RNA modification patterns

Abstract

<abstract><p><italic>Background:</italic> Multiple types of RNA modifications are associated with the prognosis of hepatocellular carcinoma (HCC) patients. However, the overall mediating effect of RNA modifications on the tumor microenvironment (TME) and the prognosis of patients with HCC is unclear. <italic>Methods:</italic> Thoroughly analyze the TME, biological processes, immune infiltration and patient prognosis based on RNA modification patterns and gene patterns. Construct a prognostic model (RNA modification score, RNAM-S) to predict the overall survival (OS) in HCC patients. Analyze the immune status, cancer stem cell (CSC), mutations and drug sensitivity of HCC patients in both the high and low RNAM-S groups. Verify the expression levels of the four characteristic genes of the prognostic RNAM-S using in vitro cell experiments. <italic>Results:</italic> Two modification patterns and two gene patterns were identified in this study. Both the high-expression modification pattern and the gene pattern exhibited worse OS. A prognostic RNAM-S model was constructed based on four featured genes (KIF20A, NR1I2, NR2F1 and PLOD2). Cellular experiments suggested significant dysregulation of the expression levels of these four genes. In addition, validation of the RNAM-S model using each data set showed good predictive performance of the model. The two groups of HCC patients (high and low RNAM-S groups) exhibited significant differences in immune status, CSC, mutation and drug sensitivity. <italic>Conclusion:</italic> The findings of the study demonstrate the clinical value of RNA modifications, which provide new insights into the individualized treatment for patients with HCC.</p></abstract>