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 role in tumor progression and immune regulation. However, the function of palmitoylation-related long non-coding RNAs (lncRNAs) in HCC remains unclear. Using The Cancer Genome Atlas (TCGA) data, we identified key palmitoylation-related lncRNAs and developed a prognostic model based on NRAV and AL031985.3. Patients were stratified into high- and low-risk groups. Immune cell infiltration, immune checkpoint gene expression, tumor mutation burden (TMB), and drug sensitivity were analyzed. Furthermore, quantitative reverse transcription polymerase chain reaction (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 exhibited increased Treg cells and immune checkpoint expression, indicating an immunosuppressive phenotype. Functional enrichment analysis revealed associations with cell cycle, immune response, and inflammatory pathways. Combining TMB with the risk score improved prognostic accuracy. Both NRAV and AL031985.3 were significantly up-regulated in tumor tissues compared to normal liver tissues, confirming their diagnostic and prognostic potential. NRAV and AL031985.3 represent promising prognostic biomarkers and immunotherapy targets in HCC. This study provides novel insights into the role of palmitoylation-related lncRNAs in HCC immune regulation.