Article Data

  • Views 235
  • Dowloads 134

Original Research

Open Access

Identification of immune-related genes for Hepatocellular Carcinoma: a study based on TCGA data

  • Chun-Bo Li1
  • Hui-Feng Wang1
  • Zheng-Kai Feng2
  • Yu-Bin Fu2
  • Jian Zhang1
  • Jing-Yi Qin1

1Department of General Surgery, People’s Hospital of Henan University of Chinese Medicine, 450003 Henan Province, P. R. China

2Department of General Surgery, The first Clinical College of Zhengzhou University, Zhengzhou City, 450003 Henan Province, P. R. China

DOI: 10.31083/jomh.2021.028 Vol.17,Issue 2,April 2021 pp.101-113

Published: 08 April 2021

*Corresponding Author(s): Jing-Yi Qin E-mail: jyqin9653@126.com

PDF (4.38 MB)

Abstract

Background and objective: Hepatocellular Carcinoma (HCC) is frequently diagnosed at the advanced stage and current treatment methods are marginally effective. The immune system is critical for the development of HCC. However, the interplay between the immune system and HCC is not well illustrated. Hence, the aim of our work was to investigate the relationship between HCC and the abnormal immune gene expression to study the potential mechanism.

Material and methods: We downloaded RNA-seq data from TCGA database, identified differentially expressed genes (DEGs) using the edgeR package, and overlapped DEGs and immune-related genes from the InnateDB website to obtain immune-related DEGs. After survival analysis, the immune-related DEGs that were significantly related to prognosis were analyzed by the STRING tool to construct PPI network. The genes in two significant PPI network modules identified by MCODE plugin were investigated by functional enrichment analysis and tumor-infiltration analysis.

Results: 68 immune-related DEGs were found to be significantly associated with prognosis in HCC, and then a PPI network was constructed. The genes in two significant PPI network modules were enriched in 31 biological processes of GO (e.g. regulation of complement activation, extracellular matrix disassembly) and 12 KEGG pathways (e.g. complement and coagulation cascades, cell cycle, proteoglycans in cancer), which were highly involved in HCC. Furthermore, we obtained 7 genes whoes expressions were significantly associated with immune infiltration levels, including E2F1, PLK1, MMP9, CDKN2A, BIRC5, CCNA2 and DCN, and 8 genes whoes copy number variations were significantly related to immune cell infiltrations, including C8A, C8B, E2F1, C6, C7, BIRC5, CCNA2 and CFB.

Conclusions: These findings contribute to understand the mechanism of HCC and provide a direction for further research on the immunotherapy of HCC.

Keywords

Hepatocellular Carcinoma; Immune cells; Immunotherapy; TCGA; GO; KEGG

Cite and Share

Chun-Bo Li,Hui-Feng Wang,Zheng-Kai Feng,Yu-Bin Fu,Jian Zhang,Jing-Yi Qin. Identification of immune-related genes for Hepatocellular Carcinoma: a study based on TCGA data. Journal of Men's Health. 2021. 17(2);101-113.

References

[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians. 2018; 68: 394-424.

[2] Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, et al. Hepatocellular carcinoma. Nature Reviews Disease Primers. 2016; 2: 16018.

[3] Liu C, Chen K, Chen P. Treatment of liver cancer. Cold Spring Harbor Perspectives in Medicine. 2015; 5: a021535.

[4] Wang H, Lu Z, Zhao X. Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer. Journal of Hematology & Oncology. 2019; 12: 133.

[5] Anwanwan D, Singh SK, Singh S, Saikam V, Singh R. Challenges in liver cancer and possible treatment approaches. Biochimica et Biophysica Acta - Reviews on Cancer. 2020; 1873: 188314.

[6] Yim SY, Kang SH, Shin JH, Jeong YS, Sohn BH, Um SH, et al. Low ARID1A expression is associated with poor prognosis in hepatocellular carcinoma. Cells. 2020; 9: 2002.

[7] Sugie T. Immunotherapy for metastatic breast cancer. Chinese Clinical Oncology. 2018; 7: 28.

[8] Zhang H, Wu D, Jin M. GCDH contributes to better outcome and acts on chemoresistance and immune exclusion in cervical cancer. European Journal of Gynaecological Oncology. 2019; 40: 831-838.

[9] Wedekind MF, Denton NL, Chen C, Cripe TP. Pediatric cancer immunotherapy: opportunities and challenges. Pediatric Drugs. 2018; 20: 395-408.

[10] Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011; 331: 1565-1570.

[11] Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annual Review of Immunology. 2011; 29: 235-271.

[12] Mittal D, Gubin MM, Schreiber RD, Smyth MJ. New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Current Opinion in Immunology. 2014; 27: 16-25.

[13] Pardee AD, Butterfield LH. Immunotherapy of hepatocellular carci-noma: Unique challenges and clinical opportunities. Oncoimmunol-ogy. 2012; 1: 48-55.

[14] Li S, Yang F, Ren X. Immunotherapy for hepatocellular carcinoma. Drug Discoveries & Therapeutics. 2015; 9: 363-371.

[15] Morgan BP, Harris CL. Complement, a target for therapy in inflamma-tory and degenerative diseases. Nature Reviews Drug Discovery. 2015; 14: 857-877.

[16] Bajic G, Degn SE, Thiel S, Andersen GR. Complement activation, regulation, and molecular basis for complement-related diseases. The EMBO Journal. 2015; 34: 2735-2757.

[17] Bishayee A. The role of inflammation and liver cancer. Advances in Experimental Medicine and Biology. 2014; 816: 401-435.

[18] Kuzet S, Gaggioli C. Fibroblast activation in cancer: when seed fertilizes soil. Cell and Tissue Research. 2016; 365: 607-619.

[19] Satyam A, Graef ER, Lapchak PH, Tsokos MG, Dalle Lucca JJ, Tsokos GC. Complement and coagulation cascades in trauma. Acute Medicine & Surgery. 2019; 6: 329-335.

[20] Sherr CJ. Cancer cell cycles. Science. 1996; 274: 1672-1677.

[21] Baghy K, Tátrai P, Regős E, Kovalszky I. Proteoglycans in liver cancer. World Journal of Gastroenterology. 2016; 22: 379-393.

[22] Farra R, Grassi G, Tonon F, Abrami M, Grassi M, Pozzato G, et al. The role of the transcription factor E2F1 in hepatocellular carcinoma. Current Drug Delivery. 2017; 14: 272-281.

[23] Liu Z, Sun Q, Wang X. PLK1, a potential target for cancer therapy. Translational Oncology. 2017; 10: 22-32.

[24] Xu L, Zhu Y, Shao J, Chen M, Yan H, Li G, et al. Dasatinib synergises with irinotecan to suppress hepatocellular carcinoma via inhibiting the protein synthesis of PLK1. British Journal of Cancer. 2017; 116: 1027-1036.

[25] Niu H, Li F, Wang Q, Ye Z, Chen Q, Lin Y. High expression level of MMP9 is associated with poor prognosis in patients with clear cell renal carcinoma. PeerJ. 2018; 6: e5050.

[26] Padhi SS, Roy S, Kar M, Saha A, Roy S, Adhya A, et al. Role of CDKN2a/p16 expression in the prognostication of oral squamous cell carcinoma. Oral Oncology. 2017; 73: 27-35.

[27] Li F, Aljahdali I, Ling X. Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study? Journal of Experimental & Clinical Cancer Research. 2019; 38: 368.

[28] Gao T, Han Y, Yu L, Ao S, Li Z, Ji J. CCNA2 is a prognostic biomarker for ER+ breast cancer and tamoxifen resistance. PLoS ONE. 2014; 9: e91771.

[29] Zhang Q, Lou Y, Bai X, Liang T. Immunometabolism: a novel perspective of liver cancer microenvironment and its influence on tumor progression. World Journal of Gastroenterology. 2018; 24: 3500-3512.

[30] Domingues P, González-Tablas M, Otero Á, Pascual D, Miranda D, Ruiz L, et al. Tumor infiltrating immune cells in gliomas and meningiomas. Brain, Behavior, and Immunity. 2016; 53: 1-15.

[31] He J, LZ, L. Wang, S. Zhuang. Effects of regulatory T cells, natural killer cells, and natural killer T cells on immunosuppression therapy in patients with recurrent embryo implantation failure. Clinical and Experimental Obstetrics & Gynecology. 2019; 46: 606-610.

[32] Eggert T, Wolter K, Ji J, Ma C, Yevsa T, Klotz S, et al. Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression. Cancer Cell. 2016; 30: 533-547.

[33] Yeung OWH, Lo C, Ling C, Qi X, Geng W, Li C, et al. Alternatively ac-tivated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma. Journal of Hepatology. 2015; 62: 607-616.

[34] Capece D, Fischietti M, Verzella D, Gaggiano A, Cicciarelli G, Tessi-tore A, et al. The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for tumor-associated macrophages. BioMed Research International. 2013; 2013: 187204.

Abstracted / indexed in

Science Citation Index Expanded Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Social Sciences Citation Index Social Sciences Citation Index contains over 3,400 journals across 58 social sciences disciplines, as well as selected items from 3,500 of the world’s leading scientific and technical journals. More than 9.37 million records and 122 million cited references date back from 1900 to present.

Current Contents - Social & Behavioral Sciences Current Contents - Social & Behavioral Sciences provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in the social and behavioral sciences.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

SCOPUS Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

DOAJ DOAJ is a community-curated online directory that indexes and provides access to high quality, open access, peer-reviewed journals.

CrossRef Crossref makes research outputs easy to find, cite, link, assess, and reuse. Crossref committed to open scholarly infrastructure and collaboration, this is now announcing a very deliberate path.

Portico Portico is a community-supported preservation archive that safeguards access to e-journals, e-books, and digital collections. Our unique, trusted process ensures that the content we preserve will remain accessible and usable for researchers, scholars, and students in the future.

Submission Turnaround Time

Conferences

    Top