Identification of palmitoylation-related lncRNAs as prognostic biomarkers and immune modulators in liver cancer

Abstract Hepatocellular carcinoma (HCC) has a high mortality rate. Current immunotherapy and targeted treatments have limited effectiveness. Palmitoylation, a reversible lipid modification, is increasingly recognized for its roles in tumor progression and immune regulation. However, the function of palmitoylation-related long non-coding RNAs (lncRNAs) in HCC remains unclear. Using TCGA data, we identified key palmitoylation-related lncRNAs and developed a prognostic model based on NRAV and AL031985.3. Patients were divided into high- and low-risk groups. Immune cell infiltration, immune checkpoint gene expression, tumor mutation burden (TMB), and drug sensitivity were analyzed. Furthermore, qRT-PCR was performed to validate lncRNA expression in clinical liver tissue samples from healthy organ donors (normal liver) and HCC patients (tumor tissue). The model effectively distinguished survival differences. High-risk patients showed increased Treg cells and immune checkpoint expression, indicating an immunosuppressive phenotype. Functional enrichment revealed associations with cell cycle, immune response, and inflammation pathways. Combining TMB with the risk score improved prognostic accuracy. Both NRAV and AL031985.3 were significantly upregulated in tumor tissues compared to normal liver tissues, confirming their diagnostic and prognostic potential. NRAV and AL031985.3 are promising prognostic biomarkers and immunotherapy targets in HCC. This study provides new insights into the role of palmitoylation-related lncRNAs in liver cancer immune regulation.