Prognostic analysis of RAS-related lncRNAs in liver hepatocellular carcinoma

BACKGROUND: Liver hepatocellular carcinoma (LIHC), whose incidence is increasing globally, is one of the most prevalent malignant cancers. RAS-related pathways are involved in the cell proliferation, migration, apoptosis, and metabolism in LIHC. Long noncoding RNAs (lncRNAs) also play important roles in the progression and prognosis of LIHC. However, the clinical role, prognostic significance, and immune regulation of RAS-related lncRNAs in LIHC remains unclear. Our study aims to construct and validate a RAS-related lncRNA prognostic risk signature that can estimate the prognosis and response to immunotherapy in LIHC. METHODS: The clinical information and corresponding messenger RNA (mRNA)/lncRNA expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and 502 RAS-related lncRNAs were identified by Pearson correlation analysis. A prognostic risk signature with 5 RAS-related lncRNAs was then developed based on the Cox regression and least absolute shrinkage and selection operator (LASSO) algorithm analyses. Subsequently, Kaplan-Meier survival curve, receiver operating characteristic (ROC) curve, and the nomogram were established to evaluate the predictive accuracy of the signature. In addition, the immune microenvironment, tumor mutation burden, and drug sensitivity associated with the signature were also analyzed in LIHC. RESULTS: Compared with the low-risk groups, the high-risk groups had an unfavorable outcome. Multivariate regression analysis revealed that the risk score signature was the independent prognostic factor superior to the other clinical variables. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses demonstrated that the risk score was highly associated with the nuclear division, DNA replication, and immune response. The group with high risk tended to hold a lower immune escape rate and better immunotherapy efficacy, while the group with low risk was more sensitive to some small molecular targeted drugs. CONCLUSIONS: We developed a RAS-related lncRNA risk signature that was highly associated with the prognosis and response to immunotherapy and targeted drugs and which provided novel mechanistic insights into the personalized treatment and potential drug selection for patients with LIHC.