Abstract
With the increasing prevalence of Hepatocellular carcinoma (HCC) and the poor prognosis of immunotherapy, reliable immune-related gene pairs (IRGPs) prognostic signature is required for personalized management and treatment of patients. Gene expression profiles and clinical information of HCC patients were obtained from the TCGA and ICGC databases. The IRGPs are constructed using immune-related genes (IRGs) with large variations. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct IRGPs signature. The IRGPs signature was verified through the ICGC cohort. 1,309 IRGPs were constructed from 90 IRGs with high variability. We obtained 50 IRGPs that were significantly connected to the prognosis and constructed a signature that included 17 IRGPs. In the TCGA and ICGC cohorts, patients were divided into high and low-risk patients by the IRGPs signature. The overall survival time of low-risk patients is longer than that of high-risk patients. After adjustment for clinical and pathological factors, multivariate analysis showed that the IRGPs signature is an independent prognostic factor. The Receiver operating characteristic (ROC) curve confirmed the accuracy of the signature. Besides, gene set enrichment analysis (GSEA) revealed that the signature is related to immune biological processes, and the immune microenvironment status is distinct in different risk patients. The proposed IRGPs signature can effectively assess the overall survival of HCC, and provide the relationship between the signature and the reactivity of immune checkpoint therapy and the sensitivity of targeted drugs, thereby providing new ideas for the diagnosis and treatment of the disease.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the leading cause of cancer-related deaths, and its morbidity and mortality are increasing (Forner et al, 2018; Villanueva, 2019)
The results showed that there were differences in the distribution of tumor tissue and normal tissue in the two data sets, which could be used for further analysis (Supplementary Figures S1A,C). 231 differential IRGs were identified in the the cancer genome atlas (TCGA) cohort and 172 differential IRGs were identified in the international cancer genome consortium (ICGC) cohort (Supplementary Figures S1B,D)
These results indicate that immune-related biological processes may play an indispensable role in the development of HCC
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the leading cause of cancer-related deaths, and its morbidity and mortality are increasing (Forner et al, 2018; Villanueva, 2019). Breakthroughs in the diagnosis and treatment of HCC have been made in recent years, the prognostic outcome of patients remains poor (Yang et al, 2019). The current clinical application of immunotherapy in HCC has benefited some patients, but this approach has not effectively improved the prognosis, and the long-term survival rate is still very poor (Dong et al, 2020). Due to the complexity and heterogeneity of HCC, individualized decision-making plans are required in diagnosis and treatment. It is necessary to identify the novel prognostic signature of HCC and use it to guide clinical treatment as an effective way to improve the prognosis of patients
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