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Identification of Prognostic Genes in the Tumor Microenvironment of Hepatocellular Carcinoma.

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机构： [1]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China, [2]South Sichuan Institute of Translational Medicine, Luzhou, China, [3]Department of Oncology and Hematology, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, China, [4]Neijiang Health and Health Vocational College, Neijiang, China, [5]Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, China, [6]Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China, [7]School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China, [8]Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China

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关键词： tumor microenvironment Hepatocellular carcinoma TCGA ESTIMATE algorithm Prognosis

摘要：

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The efficacy of immunotherapy usually depends on the interaction of immunomodulation in the tumor microenvironment (TME). This study aimed to explore the potential stromal-immune score-based prognostic genes related to immunotherapy in HCC through bioinformatics analysis. Methods: ESTIMATE algorithm was applied to calculate the immune/stromal/Estimate scores and tumor purity of HCC using the Cancer Genome Atlas (TCGA) transcriptome data. Functional enrichment analysis of differentially expressed genes (DEGs) was analyzed by the Database for Annotation, Visualization, and Integrated Discovery database (DAVID). Univariate and multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed for prognostic gene screening. The expression and prognostic value of these genes were further verified by KM-plotter database and the Human Protein Atlas (HPA) database. The correlation of the selected genes and the immune cell infiltration were analyzed by single sample gene set enrichment analysis (ssGSEA) algorithm and Tumor Immune Estimation Resource (TIMER). Results: Data analysis revealed that higher immune/stromal/Estimate scores were significantly associated with better survival benefits in HCC within 7 years, while the tumor purity showed a reverse trend. DEGs based on both immune and stromal scores primarily affected the cytokine-cytokine receptor interaction signaling pathway. Among the DEGs, three genes (CASKIN1, EMR3, and GBP5) were found most significantly associated with survival. Moreover, the expression levels of CASKIN1, EMR3, and GBP5 genes were significantly correlated with immune/stromal/Estimate scores or tumor purity and multiple immune cell infiltration. Among them, GBP5 genes were highly related to immune infiltration. Conclusion: This study identified three key genes which were related to the TME and had prognostic significance in HCC, which may be promising markers for predicting immunotherapy outcomes. Copyright © 2021 Xiang, Li, Shen, Zhao, Wu, Li, Yang, Kaboli, Du, Zheng, Wen, Cho, Yi and Xiao.

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出版当年[2021]版：

大类 | 2 区

医学

小类 | 2 区免疫学

最新[2023]版：

大类 | 2 区医学

小类 | 2 区免疫学

第一作者：

第一作者机构： [1]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China, [2]South Sichuan Institute of Translational Medicine, Luzhou, China,

共同第一作者：

通讯作者：

通讯机构： [1]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China, [8]Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China

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Identification of Prognostic Genes in the Tumor Microenvironment of Hepatocellular Carcinoma.

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