Construction of an m6A- and neutrophil extracellular traps-related lncRNA model to predict hepatocellular carcinoma prognosis and immune landscape.

ABSTRACT

Purpose: To investigate the impact of N6-methyladenosine- (m6A) and neutrophil extracellular traps- (NETs) related lncRNAs (MNlncRNAs) on the prognosis of hepatocellular carcinoma (HCC). Methods: We collected m6A and NETs-related genes from published studies. We identified the MNlncRNAs by correlation analysis. Cox regression and the least absolute selection operator (LASSO) method were used to select predictive MNlncRNAs. The expressions of predictive MNlncRNAs were detected by cell and tissue experiments. Survival, medication sensitivity, and immunological microenvironment evaluations were used to assess the model's prognostic utility. Finally, we performed cellular experiments to further validate the model's prognostic reliability. Results: We obtained a total of 209 MNlncRNAs. 7 MNlncRNAs comprised the prognostic model, which successfully stratifies HCC patients, with the area under the curve (AUC) ranging from 0.7 to 0.8. In vitro tests confirmed that higher risk patients had worse prognosis. Risk score, immunological microenvironment, and immune checkpoint gene expression were all significantly correlated with each other in HCC. In the group at high risk, immunotherapy could be more successful. Cellular assays confirmed that HCC cells with high risk scores have a higher proliferation and invasive capacity. Conclusion: The MNlncRNAs-related prognostic model aided in determining HCC prognosis, revealing novel therapeutic options, notably immunotherapy.