Identification of immune-related lncRNA signature for predicting immune checkpoint blockade and prognosis in hepatocellular carcinoma

Background: An increasing body of evidence has supported that long non-coding RNAs (lncRNAs) can play as essential roles of various physiological process and pathological diseases. We aimed to construct a robust immune-associated lncRNA signature associated with the prognosis for HCC survival prediction. Methods: 7 immune-associated lncRNAs presenting significant correlation with survival were screened through stepwise univariate Cox regression and LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, proportional hazards model, and ROC analyses further conducted. Gene set enrichment analysis (GSEA) was applied for functional annotation. We conducted quantitative real-time polymerase chain reaction to determine NRAV expression and preliminarily explored the latent role of NRAV in prognosis of HCC patients. Results: Finally, 7 immune-related lncRNA signature composed of AC007405.3, AC023157.3, NRAV, CASC19, MSC-AS1, GASAL1, and LINC00942 were validated. This lncRNAs signature can serve as an independent predictive biomolecular factor. This signature was further confirmed in the validation group and the entire cohort. We demonstrated that NRAV was significantly upregulated in HCC cell lines and it may serve as a key regulator in HCC. Our signature was associated to apoptosis and immunologic characteristics. This signature mediated immune cell infiltration (i.e., Dendritic, etc.,) and immune checkpoint blockade (ICB) immunotherapy-related molecules (i.e., CD274, etc.,). Conclusion: This immune-related lncRNA signature possesses promising prognostic value in HCC and may have the potentiality to predict clinical outcome of ICB immunotherapy.