Cuproptosis-Related lncRNA Risk Model for Hepatocellular Carcinoma Prognosis and Immunotherapy Response

Background: Cuproptosis is a type of cell death caused by copper imbalance associated with the growth and proliferation of cancer cells. Long noncoding RNAs (lncRNAs) play a crucial role in hepatocellular carcinoma (HCC) development. Here, we aimed to investigate the role of cuproptosis-related lncRNAs in the clinical prognostic prediction and immunotherapy for HCC. Methods: A correlation network between lncRNAs and cuproptosis-related genes in HCC was constructed by conducting co-expression and Cox regression analyses. LASSO-Cox analysis was used to obtain lncRNAs that constitute the cuproptosis-associated lncRNA signature, which was then used to predict patient prognosis and immunotherapy response. To verify the clinical applicability of the risk model, a nomogram was constructed and an anti-neoplastic drug sensitivity analysis was performed. Results: Four cuproptosis-related lncRNAs (AL590705.3, SPRY4-AS1, AC135050.5, and AL031985.3) were identified and used to develop a prognostic signature for HCC. Based on the four lncRNAs, a risk prediction model was established. For overall survival (OS) in HCC patients, the area under the ROC curve (AUC) for the risk score was 0.715, outperforming traditional clinical factors such as age (AUC=0.531), gender (AUC=0.509), and stage (AUC=0.671). High-risk patients had worse overall survival, progression-free survival, and higher mortality. Independent ROC analysis, nomogram‐based modeling, and concordance index analysis indicated that the risk model has high predictive accuracy for HCC. Conclusions: This model demonstrates potential in predicting prognosis, and offers novel insights to the treatment and management of HCC. Our study suggests that lncRNAs may serve as a novel biomarker and potential therapeutic target for HCC.