An immunogenic cell death-associated gene signature predicts prognosis in hepatocellular carcinoma

Abstract

Abstract Background: Liver cancer is the third leading cause of cancer-related mortality in the world, and hepatocellular carcinoma (HCC) accounts for approximately 90% of the incidence of all liver cancers. Methods: The TCGA-LIHC datasets were obtained from TCGA database, LIRI-JP datasets were obtained from ICGC database and immunogenic cell death (ICD) genes were obtained from previous literature. WGCNA analysis identifies ICD-associated genes. Functional analysis was used to investigate the biological characteristics of ICD-associated genes. Univariate cox analysis and least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to select prognostic ICD-associated genes and constructed a prognostic risk score. Prognostic independence of ICD risk scores was determined by univariate and multivariate cox regression analyses. Then constructed a nomogram and the diagnostic value was assessed using the decision curve analysis. Immune infiltration analysis and drug sensitivity analysis were used to investigate immune cell enrichment and drug response in HCC patients who were classified as low- or high-risk based on their risk score. Results: Most of ICD genes were differentially expressed in normal and HCC patients, and some ICD genes were differentially expressed in different clinical groups. A total of 185 ICD-associated genes were identified by WGCNA. A nine-gene-based (CSN1S1, FGF9, PNLIPRP2, ISM2, FKBP6, BTNL9, CLEC3B, RAMP3, and SRL) prognostic risk score was developed. Based on the risk score, training cohort were divided into low- and high-risk groups, patients in the low-risk group had a better prognosis, and external independent data verified the reliability of the model. Univariate and multivariate Cox regression analysis showed independent prognostic factors for OS of ICD risk score. Diagnostic nomogram was constructed to predict prognosis. Immune infiltration analysis showed that some innate and adaptive immune cells were significantly different between low- and high-risk groups, Conclusion: We developed and validated a novel prognostic predictive classification system for HCC based on nine ICD-associated genes. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of HCC patients.