Identification of RUNX1 and IFNGR2 as prognostic-related biomarkers correlated with immune infiltration and subtype differentiation of low-grade glioma

Authors

  • Xia Zhang Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China https://orcid.org/0000-0003-1682-121X
  • Hongyu Chu Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing, China; School of Rehabilitation, Capital Medical University, Beijing, China
  • Yuan Cheng Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
  • Jie Ren Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
  • Wei Wang Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
  • Xicheng Liu Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
  • Xiaodong Yan School of Clinical Medicine, Jining Medical University, Jining, China

DOI:

https://doi.org/10.17305/bjbms.2022.8086

Keywords:

Runt-related transcription factors (RUNXs), low-grade glioma (LGG), interferon-gamma receptor 2 (IFNGR2), tumor microenvironment (TME), immune infiltration, immune checkpoints

Abstract

Immune cell infiltration occurs in the tumor microenvironment (TME) and influences cancer progression through interaction with tumor cells. Runt-related transcription factors (RUNXs), RUNX1-3, are the master regulators of development and differentiation and are all important to the development of immune cells. However, the role of RUNXs in the immune cells of TME remains unclear. In this study, we first used online related databases and related LGG data from TCGA and CGGA to conduct bioinformatics analysis, which confirmed that RUNXs were significantly and positively correlated with immune infiltration in multiple tumors, especially in low-grade glioma (LGG) and there was the highest correlation between RUNXs and the progress and prognosis of LGG. Furthermore, the functional enrichment analysis revealed that RUNXs might be involved in the inflammatory and immune responses of the biological processes, and RUNXs were tightly associated with the multiple immune checkpoint molecules. Subsequent results confirmed that RUNX1, as an independent prognostic factor for LGG, may target interferon-gamma receptor 2 (IFNGR2) to regulate glioma cell proliferation, invasion, and migration. Besides, we also found that the expression levels of RUNX1 and IFNGR2 were significantly reduced, and their correlation was enhanced in the IDH-mutant subtype. Patients with a high expression of RUNX1 and/or IFNGR2 (HH/H) in the IDH-mutant subtype showed poorer prognosis and significantly increased infiltration of M2 macrophages. This finding implied the possible key role of RUNX1 in the differentiation of IDH mutant subtypes as well as in the formation of tumor microenvironment (TME) infiltration signatures by monitoring IFNGR2.

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Author Biography

  • Xia Zhang, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China

    Education

    9/2018-Present

    Ph.D. Candidate, Physiology, Capital Medical University, Beijing, China,

     

    9/2013-6/2017

    B.S. Nursing, Nanjing University of Chinese Medicine, Nanjing, China,

    Research Interests

    • Regulation of autophagosome-lysosomal machinery on acute ischemic stroke
    • Molecular mechanism of occurrence and development of colorectal cancer

     

    Honors and Awards

    9/2020-Present

     

    Science and Technology Award of Capital Medical University

    (Second prize, Ranked 4/5)

    • National Scholarship for doctoral students

    • Postgraduate Academic Scholarships (Two times)

    9/2018-6/2020

    • Postgraduate Academic Scholarships (Two times)

    9/2013-6/2017

    • Outstanding Graduates

    • National Encouragement scholarship (Three times)

    • Outstanding Volunteer

    • Peeli Scholarship of JiangSu Tao Shing Pee Education Foundation (Four times)

     

    Publications (#equal contribution)

    1) Zhang X#, Wei M#, Fan J, Yan W, Zha X, Song H, Wan R, Yin Y, Wang W. Ischemia-induced upregulation of autophagy preludes dysfunctional lysosomal storage and associated synaptic impairments in neurons. Autophagy. 2021;17(6):1519-1542. doi: 10.1080/15548627.2020.1840796. (cited 57 times, cover image).

    2) Yan W, Fan J, Zhang X, Song H, Wan R, Wang W, Yin Y. Decreased neuronal synaptosome associated protein 29 contributes to poststroke cognitive impairment by disrupting presynaptic maintenance. Theranostics. 2021;11(10):4616-4636. doi:10.7150/thno.54210.

    3) Xiaodong Yan#, Yuan Cheng#, Xia Zhang#, Yi Hu, Haixia Huang, Jie Ren, Boye Wen, Yuhui Yang, Keyuan Xiao, Wenqing Hu, Wei Wang. NICD3 regulates the expression of MUC5AC and MUC2 by recruiting SMARCA4 and is involved in the differentiation of mucinous colorectal adenocarcinoma. Molecular Oncology. 2022. (Major Revision, 09-Feb-2022)

    4) Jiahui Fan, Huimeng Song, Xia Zhang, Weijie Yan, Song Han, Yanling Yin. Acute ischemia-induced reduction of Sirt3 protein levels in neurons contributed to neuronal injuries via a mitochondrion-associated manner. Acta Physiologica Sinica. 2021;73(01):17-25. DOI:10.13294/j.aps.2021.0008. doi:10.13294/j.aps.2021.0008. (Chinese core).

    5) Zhang Xia, Chen Lixia, Li Qiuling, et al. Investigation and Intervention Measures of College Students Lifestyle in Medical Colleges and Universities. China Journal of Health Psychology. 2016. doi:10.13342/j.cnki.cjhp.2016.07.029. (Chinese, cited 6 times).

    6) Zhang Xia, Chen Lixia, Du Shizheng. Research Progress of Adolescent Mobile phone dependence at home and abroad. Chinese Journal of School Health. 2016. doi:10.16835/j.cnki.1000-9817.2016.11.053. (Chinese core, cited 30 times).

    Conference Presentations

    1) The 2nd Capital Medical College Graduate academic Forum and Beijing-Tianjin-Hebei Medical Graduate academic Forum (Beijing). January, 2021. Oral Presentation and Poster.

    2) The 3rd China Conference on Autophagy (ShenZhen). April, 2021. Poster presentation.

    Invited Manuscript Reviewer

    1) Bosnian Journal of Basic Medical Sciences (BJBMS)

Identification of RUNX1 and IFNGR2  as prognostic-related biomarkers correlated  with immune infiltration and subtype  differentiation of low-grade glioma

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Published

01-05-2023

How to Cite

1.
Identification of RUNX1 and IFNGR2 as prognostic-related biomarkers correlated with immune infiltration and subtype differentiation of low-grade glioma. Biomol Biomed [Internet]. 2023 May 1 [cited 2024 Apr. 21];23(3):405–425. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/8086