4.6 Article

Development and Verification of an Immune-Related Gene Pairs Prognostic Signature in Hepatocellular Carcinoma

Journal

FRONTIERS IN MOLECULAR BIOSCIENCES
Volume 8, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.715728

Keywords

hepatocellular carcinoma; immune-related gene pairs; prognosis; tumor immune environment; targeting therapy

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The study focuses on constructing a prognostic signature using immune-related gene pairs (IRGPs) to assess overall survival in patients with Hepatocellular carcinoma (HCC). The signature not only provides insights into the immune checkpoint therapy responsiveness and drug sensitivity, but also offers new strategies for personalized management and treatment of the disease.
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.

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