Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Thursday, 12 / 09 / 2021

Abstract

ORIGINAL ARTICLE

Integrative Characterization of Immune-relevant Genes in Hepatocellular Carcinoma

Wei-Feng Hong1,#, Yu-Jun Gu2,#, Na Wang3,#, Jie Xia3, Heng-Yu Zhou3,4, Ke Zhan5, Ming-Xiang Cheng6and Ying Cai3,7,*

1  Department of Medical Imaging, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
2  Department of Ultrasonic Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
3  Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
4  College of Nursing, Chongqing Medical University, Chongqing, China
5  Department of Gastroenterology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
6  Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
7  Department of Intensive Care Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
7  Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
#These authors contributed equally to this study.
*Correspondence to: Ying Cai, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases; Department of Intensive Care Medicine, The Second Affiliated Hospital, Chongqing Medical University, 1# Yixueyuan Road, Yuzhong District, Chongqing 400000, China. ORCID:  https://orcid.org/0000-0002-1782-719X . Tel: +86-15923330181, E-mail:This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2021;9(3):301-314 DOI: 10.14218/JCTH.2020.00132
Received: November 27, 2020 Accepted: February 21, 2021 Published online: March 8, 2021

Abstract

Background and Aims:Tumor microenvironment plays an essential role in cancer development and progression. Cancer immunotherapy has become a promising approach for the treatment of hepatocellular carcinoma (HCC). We aimed to analyze the HCC immune microenvironment characteristics to identify immune-related genetic changes.

Methods: Key immune-relevant genes (KIRGs) were obtained through integrating the differentially expressed genes of The Cancer Genome Atlas, immune genes from the Immunology Database and Analysis Portal, and immune differentially expressed genes determined by single-sample gene set enrichment analysis scores. Cox regression analysis was performed to mine therapeutic target genes. A regulatory network based on KIRGs, transcription factors, and immune-related long non-coding RNAs (IRLncRNAs) was also generated. The outcomes of risk score model were validated in a testing cohort and in clinical samples using tissue immunohistochemistry staining. Correlation analysis between risk score and immune checkpoint genes and immune cell infiltration were investigated.

Results:In total, we identified 21 KIRGs, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), and found IKBKE, IL2RG, EDNRA, and IGHA1 may be equally important to PD-1 or CTLA4. Meanwhile, KIRGs, various transcription factors, and IRLncRNAs were integrated to reveal that the NRF1-AC127024.5-IKBKE axis might be involved in tumor immunity regulation. Furthermore, the immune-related risk score model was established according to KIRGs and key IRLncRNAs, and verified more obvious discriminating power in the testing cohort. Correlation analysis indicated TNFSF4 , LGALS9 , KIAA1429 , IDO2, and CD276 were closely related to the risk score, and CD4 T cells, macrophages, and neutrophils were the primary immune infiltration cell types.

Conclusions:Our results highlight the importance of immune genes in the HCC microenvironment and further unravel the underlying molecular mechanisms in the development of HCC.

Keywords

Hepatocellular carcinoma, Immune gene, Immunotherapy, Tumor microenvironment, Risk model

Journal of Clinical and Translational Hepatology 2021 vol. 9, 301-314  [ Html  ] [ PDF Full-text ]

© 2021 Authors. This is an Open Access article distributed under the terms of the  Creative Commons Attribution-Noncommercial 4.0 License(CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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