A novel gene signature based on endoplasmic reticulum stress for overall survival prediction for patients with hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) remains one of the most common human cancers, the death cases induced by HCC are increasing these years. Endoplasmic reticulum stress (ERS) occurs when misfolded proteins can't be disposed properly. It’s reported that ERS plays a crucial role in the pathogenesis of human malignant tumors. Results In our study, we established an ERS-related gene signature to predict the overall survival (OS) of HCC patients. The TCGA-LIHC cohort was used as train set while the ICGC-LIRI-JP cohort was used as validation set. A 9-genes ERS-related signature was constructed and the Riskscore was calculated according to it. The results of receiver operating characteristic curve (ROC) showed that the area under the curve (AUC) were 0.784 at 1 year, 0.780 at 2 years, 0.793 at 3 years in train set, this index in validation set were 0.694 at 1 year, 0.622 at 2 years, 0.613 at 3 years respectively. The cases in train set were grouped into high-risk group and low risk group based on the median value of Riskscore. The analysis of immune status revealed an immunosuppressive microenvironment in the high-risk group. The analysis of tumor mutation burden (TMB) and copy number variants (CNV) analysis revealed that the high-risk group patients had a higher genomic mutation frequency in low-risk group had a better prognosis than the high-risk group patients. In Univariate Cox regression analysis, the hazard ratio of Riskscore to the OS was 2.718 (95% CI: 2.173–3.399). In Multivariate Cox regression analysis, the hazard ratio of Riskscore was 2.422 (95% CI:1.805–3.25). At last, we established a nomogram according to the Riskscore and Eastern Cooperative Oncology Group (ECOG) performance status. The AUCs of the nomogram were 0.851 at 1 year, 0.860 at 2 years, 0.866 at 3 years. Conclusion In our study, a novel ERS-related gene signature was constructed to forecast the overall survival of HCC patients. This study maybe provide a new understanding of the tumorigenesis and new therapeutic targets for HCC.