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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The findings of the study demonstrate the clinical value of RNA modifications, which provide new insights into the individualized treatment for patients with HCC.

An integrative analysis reveals the prognostic value and potential functions of MTMR2 in hepatocellular carcinoma.

Abnormal expression of myotubularin-related protein 2 (MTMR2) has been identified in certain types of cancer, leading to varying effects on tumor genesis and progression. However, the various biological significances of MTMR2 in hepatocellular carcinoma (HCC) have not been systematically and comprehensively studied. The aim of this study was to explore the role of MTMR2 in HCC. We obtained the raw data from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Afterward, we analyzed the data using R and cBioPortal. We investigated the connection between MTMR2 and its expression, prognosis, clinical significance, methylation, genetic alterations, tumor microenvironment (TME), tumor mutation burden (TMB), and drug reactivity in HCC patients. MTMR2 expression levels in HCC cells were validated through western blotting and RT-qPCR. MTMR2 exhibits high levels of expression across a wide range of cancer types, including HCC. MTMR2 is diagnostically valuable in detecting HCC, with its up-regulated expression often being indicative of poor prognosis among HCC patients. The in vitro experiments confirmed elevated MTMR2 expression in HepG2, HUH-7, and MHCC-97H cells. Univariate and multivariate Cox analysis demonstrated that MTMR2 was an independent prognostic factor in HCC patients. The cg20195272 site has the highest degree of methylation in MTMR2, and it is positively correlated with MTMR2 expression. Patients with high levels of methylation at the cg20195272 site show poor prognosis. Analysis of the TME indicates that high expression of MTMR2 is associated with elevated ESTIMATE score and that MTMR2 expression correlates positively with infiltration by resting memory CD4 T cells, activated dendritic cells, as well as several immune checkpoints. There is a negative correlation between MTMR2 expression and TMB, and drug sensitivity analyses have shown that higher MTMR2 expression is associated with lower IC50 values. This study indicates that increased expression of MTMR2 may play a crucial role in the occurrence, progression, diagnosis, prognostic prediction and drug therapy of HCC.