LncRNA NRAV is associated with unfavorable prognosis and immune-related transcriptional features in hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) remains a lethal malignancy, and robust biomarkers are needed to refine risk stratification and support clinical decision-making. Long noncoding RNAs can shape tumor biology and immune states. We investigated the clinical relevance of lncRNA NRAV in HCC and its association with immune-related features. METHODS: NRAV expression and clinical associations were assessed using TCGA-LIHC, paired tumor-adjacent tissue comparisons, GTEx normal liver controls, and independent GEO cohorts. Prognostic associations were evaluated by Kaplan-Meier and Cox regression analyses. Immune features were profiled using ssGSEA and correlation analyses with immune checkpoint molecules. Functional effects of NRAV were examined in HCC cells using loss-of-function assays. RESULTS: NRAV was consistently overexpressed in HCC compared with normal liver tissues across multiple cohorts and paired tumor-normal samples. Higher NRAV expression was associated with adverse clinicopathological features and poorer overall survival. ROC analysis showed that NRAV expression had good discriminatory performance in HCC (AUC = 0.901, 95% CI: 0.865-0.937). Immune analyses showed that NRAV-high tumors were associated with reduced CD8⁺ T-cell-related signatures and increased macrophage- and Th2-associated signatures, together with elevated expression of multiple immune checkpoint molecules (e.g., PDCD1, CD274, CTLA4, LAG3, and HAVCR2). In vitro, NRAV knockdown suppressed colony formation, migration, and invasion in HCC cells. CONCLUSION: NRAV is upregulated in HCC and is associated with unfavorable prognosis, adverse clinicopathological features, and immune-related transcriptional patterns. NRAV may represent a candidate biomarker for risk assessment and warrants further mechanistic and translational investigation.