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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

IL1R2 is a Novel Prognostic Biomarker for Lung Adenocarcinoma

Author(s): Ying Zhang*, Danyu Ma, Yile Gong, Fan Wang, Jingping Wu and Chen Wu*

Volume 24, Issue 5, 2024

Published on: 23 June, 2023

Page: [620 - 629] Pages: 10

DOI: 10.2174/1566524023666230420092142

Price: $65

Open Access Journals Promotions 2
Abstract

Aims: The aim of this study is to figure out the role of IL1R2 in LUAD (lung adenocarcinoma).

Background: IL1R2, a special member of IL-1 receptor family, binds to IL-1 and plays an important role in inhibiting IL-1 pathway, which seems to be involved in tumorigenesis. Emerging studies demonstrated higher IL1R2 expression levels in several malignancies.

Objective: In the present study, we assessed the expression of IL1R2 in LUAD tissues with immunohistochemistry and explored various databases to determine whether it could be a potential prognostic biomarker and therapeutic target.

Methods: The expression level of IL1R2 in lung adenocarcinoma was analyzed by Immunohistochemistry and UALCAN database. The correlation between IL1R2 expression and the patient prognosis was identified by Kaplan-Meier plotter. The correlation of IL1R2 expression with immune infiltrates was clarified by TIMER database. The protein-protein interaction network and gene functional enrichment analysis were constructed and performed by STRING and Metascape database.

Results: Immunohistochemistry showed that the expression of IL1R2 was higher in tumor tissues of LUAD patients and that patients with lower IL1R2 level have a better prognosis than their counterparts. We validated our findings in several online databases and found that IL1R2 gene was also positively correlated with B cells and neutrophils and biomarkers of CD8+T cells and exhausted T cells. PPI network and gene enrichment analyses showed that expression of IL1R2 was also associated with complex functionspecific networks involving IL-1 signal, NF-KappaB transcription factors.

Conclusion: According to these findings, we demonstrated that IL1R2 was involved in the progression and prognosis of LUAD and the underlying mechanism needs further investigation.

Keywords: IL1R2, lung adenocarcinoma, prognosis, immune infiltration, bioinformatics analysis, biomarker.

[1]
Barta JA, Powell CA, Wisnivesky JP. Global epidemiology of lung Cancer. Ann Glob Health 2019; 85(1): 8.
[http://dx.doi.org/10.5334/aogh.2419] [PMID: 30741509]
[2]
Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 6(2): 244-85.
[http://dx.doi.org/10.1097/JTO.0b013e318206a221] [PMID: 21252716]
[3]
Saito M, Suzuki H, Kono K, Takenoshita S, Kohno T. Treatment of lung adenocarcinoma by molecular-targeted therapy and immunotherapy. Surg Today 2018; 48(1): 1-8.
[http://dx.doi.org/10.1007/s00595-017-1497-7] [PMID: 28280984]
[4]
Denisenko TV, Budkevich IN, Zhivotovsky B. Cell death based treatment of lung adenocarcinoma. Cell Death Dis 2018; 9(2): 117.
[http://dx.doi.org/10.1038/s41419-017-0063-y] [PMID: 29371589]
[5]
McMahan CJ, Slack JL, Mosley B, et al. A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. EMBO J 1991; 10(10): 2821-32.
[http://dx.doi.org/10.1002/j.1460-2075.1991.tb07831.x] [PMID: 1833184]
[6]
Molgora M, Supino D, Mantovani A, Garlanda C. Tuning inflammation and immunity by the negative regulators IL-1R2 and IL-1R8. Immunol Rev 2018; 281(1): 233-47.
[http://dx.doi.org/10.1111/imr.12609] [PMID: 29247989]
[7]
Boraschi D, Italiani P, Weil S, Martin MU. The family of the interleukin-1 receptors. Immunol Rev 2018; 281(1): 197-232.
[http://dx.doi.org/10.1111/imr.12606] [PMID: 29248002]
[8]
Liu J, Yang Y, Li H, et al. IL1R2 polymorphisms are associated with an increased risk of esophageal cancer. Curr Mol Med 2019; 20(5): 379-87.
[PMID: 31744444]
[9]
Zhang L, Qiang J, Yang X, et al. IL1R2 blockade suppresses breast tumorigenesis and progression by impairing USP15 dependent BMI1 stability. Adv Sci 2020; 7(1): 1901728.
[http://dx.doi.org/10.1002/advs.201901728] [PMID: 31921558]
[10]
Yuan M, Wang L, Huang H, et al. IL-1R2 expression in human gastric cancer and its clinical significance. Biosci Rep 2021; 41(3): BSR20204425.
[http://dx.doi.org/10.1042/BSR20204425] [PMID: 33704402]
[11]
Niu F, Wang T, Li J, et al. The impact of genetic variants in IL1R2 on cervical cancer risk among Uygur females from China: A case-control study. Mol Genet Genomic Med 2019; 7(1): e00516.
[http://dx.doi.org/10.1002/mgg3.516] [PMID: 30460760]
[12]
Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: proposals for revision of the tnm stage groupings in the forthcoming (Eighth) Edition of the TNM classification for lung cancer. J Thorac Oncol 2016; 11(1): 39-51.
[http://dx.doi.org/10.1016/j.jtho.2015.09.009] [PMID: 26762738]
[13]
Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia 2017; 19(8): 649-58.
[http://dx.doi.org/10.1016/j.neo.2017.05.002] [PMID: 28732212]
[14]
Győrffy B, Surowiak P, Budczies J, Lánczky A. Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One 2013; 8(12): e82241.
[http://dx.doi.org/10.1371/journal.pone.0082241] [PMID: 24367507]
[15]
Li T, Fan J, Wang B, et al. TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res 2017; 77(21): e108-10.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0307] [PMID: 29092952]
[16]
Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019; 10(1): 1523.
[http://dx.doi.org/10.1038/s41467-019-09234-6] [PMID: 30944313]
[17]
Fan B, Ji K, Bu Z, et al. ARHGAP11A is a prognostic biomarker and correlated with immune infiltrates in gastric cancer. Front Mol Biosci 2021; 8: 720645.
[http://dx.doi.org/10.3389/fmolb.2021.720645] [PMID: 34733886]
[18]
Mar AC, Chu CH, Lee HJ, et al. Interleukin-1 receptor type 2 acts with c-fos to enhance the expression of interleukin-6 and vascular endothelial growth factor a in colon cancer cells and induce angiogenesis. J Biol Chem 2015; 290(36): 22212-24.
[http://dx.doi.org/10.1074/jbc.M115.644823] [PMID: 26209639]
[19]
Liu X, Min L, Duan H, et al. Short hairpin RNA (shRNA) of type 2 interleukin-1 receptor (IL1R2) inhibits the proliferation of human osteosarcoma U-2 OS cells. Med Oncol 2015; 32(1): 364.
[http://dx.doi.org/10.1007/s12032-014-0364-2] [PMID: 25432697]
[20]
Freiberger SN, Cheng PF, Iotzova-Weiss G, et al. Ingenol mebutate signals via PKC/MEK/ERK in keratinocytes and induces interleukin decoy receptors IL1R2 and IL13RA2. Mol Cancer Ther 2015; 14(9): 2132-42.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0023-T] [PMID: 26116359]
[21]
Autenshlyus A, Arkhipov S, Mikhailova E, Marinkin I, Arkhipova V, Varaksin N. The relationship between cytokine production, CSF2RA, and IL1R2 expression in mammary adenocarcinoma, tumor histopathological parameters, and lymph node metastasis. Technol Cancer Res Treat 2019; 18.
[http://dx.doi.org/10.1177/1533033819883626] [PMID: 31635541]
[22]
Wang S, Liu W, Ly D, Xu H, Qu L, Zhang L. Tumor-infiltrating B cells: Their role and application in anti-tumor immunity in lung cancer. Cell Mol Immunol 2019; 16(1): 6-18.
[http://dx.doi.org/10.1038/s41423-018-0027-x] [PMID: 29628498]
[23]
Ritvo PGG, Churlaud G, Quiniou V, et al. T fr cells lack IL-2Rα but express decoy IL-1R2 and IL-1Ra and suppress the IL-1–dependent activation of T fh cells. Sci Immunol 2017; 2(15): eaan0368.
[http://dx.doi.org/10.1126/sciimmunol.aan0368] [PMID: 28887367]
[24]
Ocana A, Nieto-Jiménez C, Pandiella A, Templeton AJ. Neutrophils in cancer: Prognostic role and therapeutic strategies. Mol Cancer 2017; 16(1): 137.
[http://dx.doi.org/10.1186/s12943-017-0707-7] [PMID: 28810877]
[25]
Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: Neutral no more. Nat Rev Cancer 2016; 16(7): 431-46.
[http://dx.doi.org/10.1038/nrc.2016.52] [PMID: 27282249]
[26]
Martin P, Palmer G, Vigne S, et al. Mouse neutrophils express the decoy type 2 interleukin-1 receptor (IL-1R2) constitutively and in acute inflammatory conditions. J Leukoc Biol 2013; 94(4): 791-802.
[http://dx.doi.org/10.1189/jlb.0113035] [PMID: 23817563]
[27]
Shimizu K, Nakajima A, Sudo K, et al. IL-1 receptor type 2 suppresses collagen-induced arthritis by inhibiting IL-1 signal on macrophages. J Immunol 2015; 194(7): 3156-68.
[http://dx.doi.org/10.4049/jimmunol.1402155] [PMID: 25725107]
[28]
Guo X, Zhang Y, Zheng L, et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Nat Med 2018; 24(7): 978-85.
[http://dx.doi.org/10.1038/s41591-018-0045-3] [PMID: 29942094]
[29]
Ding X, Zhang J, Shi M, et al. High expression level of interleukin-1β is correlated with poor prognosis and PD-1 expression in patients with lung adenocarcinoma. Clin Transl Oncol 2020; 23(1): 35-42.
[PMID: 32472456]
[30]
Tian T, Lofftus S, Pan Y, et al. IL1α antagonizes IL1β and promotes adaptive immune rejection of malignant tumors. Cancer Immunol Res 2020; 8(5): 660-71.
[http://dx.doi.org/10.1158/2326-6066.CIR-19-0552] [PMID: 32161110]
[31]
Peters VA, Joesting JJ, Freund GG. IL-1 receptor 2 (IL-1R2) and its role in immune regulation. Brain Behav Immun 2013; 32: 1-8.
[http://dx.doi.org/10.1016/j.bbi.2012.11.006] [PMID: 23195532]
[32]
Zhang W, Borcherding N, Kolb R. IL-1 signaling in tumor microenvironment. Adv Exp Med Biol 2020; 1240: 1-23.
[http://dx.doi.org/10.1007/978-3-030-38315-2_1] [PMID: 32060884]

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