Prognostic Value and Immune Landscapes of Immunogenic Cell Death-related LncRNAs in Hepatocellular Carcinoma

Background: Both immunogenic cell death (ICD) and long noncoding RNAs (lncRNAs) are strongly associated with tumor development, but the mechanism of action of ICD-associated lncRNAs in hepatocellular carcinoma (HCC) remains unclear.

Methods: We collected data from 365 HCC patients from The Cancer Genome Atlas (TCGA) database. We formulated a prognostic signature of ICD-associated lncRNAs and a nomogram to predict prognosis. To explore the potential mechanisms and provide clinical guidance, survival analysis, enrichment analysis, tumor microenvironment analysis, tumor mutation burden (TMB), and drug sensitivity prediction were conducted based on the subgroups obtained from the risk score.

Results: A prognostic signature of seven ICD-associated lncRNAs was constructed. Kaplan-Meier (K-M) survival curves showed a more unfavorable outcome in high-risk patients. The nomogram had a higher predictive value than the nomogram constructed without the risk model. Enrichment analysis confirmed that risk lncRNAs were closely associated with cell proliferation and mitosis. Most of the immune checkpoints currently used in therapy (e.g., PDCD1 and CTLA4) appeared to be elevated in high-risk patients. Tumor microenvironment analysis showed differential expression of lymphocytes (including natural killer cells, regulatory T cells, etc.) in the high-risk group. TMB had a higher incidence of mutations in the high-risk group (P=0.004). Chemotherapy drug sensitivity prediction provides effective guidelines for individual therapy. RT-qPCR of human HCC tissues verified the accuracy of the model.

Conclusion: We constructed an effective prognostic signature for patients with HCC using seven ICD-lncRNAs, which provides guidance for the prognostic assessment and personalized treatment of patients.