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Endocrine

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13-08-2022 | Biomarkers | Original Article

Identification of two potential immune-related biomarkers of Graves’ disease based on integrated bioinformatics analyses

Authors: Yihan Zhang, Jia Wei, Hong Zhou, Bingxin Li, Ying Chen, Feng Qian, Jingting Liu, Xin Xie, Huanbai Xu

Published in: Endocrine | Issue 2/2022

Abstract

Background

Graves’ disease (GD) is an autoimmune disease, the incidence of which is increasing yearly. GD requires long-life therapy. Therefore, the potential immune-related biomarkers of GD need to be studied.

Method

In our study, differentially expressed genes (DEGs) were derived from the online Gene Expression Omnibus (GEO) microarray expression dataset GSE71956. Protein‒protein interaction (PPI) network analyses were used to identify hub genes, which were validated by qPCR. GSEA was used to screen potential pathways and related immune cells. Next, CIBERSORT analysis was used to further explore the immune subtype distribution pattern among hub genes. ROC curves were used to analyze the specificity and sensitivity of hub genes.

Result

44 DEGs were screened from the GEO dataset. Two hub genes, EEF1A1 and EIF4B, were obtained from the PPI network and validated by qPCR (p < 0.05). GSEA was conducted to identify potential pathways and immune cells related to these the two hub genes. Immune cell subtype analysis revealed that hub genes had extensive associations with many different types of immune cells, particularly resting memory CD4⁺ T cells. AUCs of ROC analysis were 0.687 and 0.733 for EEF1A1 and EIF4B, respectively.

Conclusion

Our study revealed two hub genes, EEF1A1 and EIF4B, that are associated with resting memory CD4⁺ T cells and potential immune-related molecular biomarkers and therapeutic targets of GD.

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Y. He, et al. Association of HLA-B and HLA-DRB1 polymorphisms with antithyroid drug-induced agranulocytosis in a Han population from northern China. Sci. Rep. 7(1), 11950 (2017). PubMedPubMedCentralCrossRef

S. De Leo, S.Y. Lee, L.E. Braverman,, Hyperthyroidism. Lancet 388(10047), 906–918 (2016)PubMedPubMedCentralCrossRef

T.J. Smith, L. Hegedus, Graves’ disease. N. Engl. J. Med. 375(16), 1552–1565 (2016)PubMedCrossRef

P.N. Taylor et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat. Rev. Endocrinol. 14(5), 301–316 (2018)PubMedCrossRef

T.F. Davies et al. Graves’ disease. Nat. Rev. Dis. Prim. 6(1), 52 (2020)PubMedCrossRef

H.T. Hao et al. Treatment of Graves’ ophthalmopathy with an in-house Phosphorus-32 source: Initial clinical observations. Exp. Ther. Med 14(4), 2795–2800 (2017)PubMedPubMedCentralCrossRef

W. Gu, S. Miller, C.Y. Chiu, Clinical metagenomic next-generation sequencing for pathogen detection. Annu Rev. Pathol. 14, 319–338 (2019)PubMedCrossRef

A. Antonelli et al. Graves’ disease: Clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy. Best. Pr. Res Clin. Endocrinol. Metab. 34(1), 101388 (2020)CrossRef

M. Limbach et al. Epigenetic profiling in CD4+ and CD8+ T cells from Graves’ disease patients reveals changes in genes associated with T cell receptor signaling. J. Autoimmun. 67, 46–56 (2016)PubMedCrossRef

10.

T.J. Smith, L. Hegedus, Graves’ disease. N. Engl. J. Med 376(2), 185 (2017)PubMed

11.

J.Q. Chen, P. Szodoray, M. Zeher, Toll-like receptor pathways in autoimmune diseases. Clin. Rev. Allergy Immunol. 50(1), 1–17 (2016)PubMedCrossRef

12.

K.A. Dvornikova et al. Polymorphism of toll-like receptor genes and autoimmune endocrine diseases. Autoimmun. Rev. 19(4), 102496 (2020)PubMedCrossRef

13.

S.Y. Han et al. High-mobility group box 1 is associated with the inflammatory pathogenesis of graves’ orbitopathy. Thyroid 29(6), 868–878 (2019)PubMedCrossRef

14.

S. Shah et al. Ras and Rap1: A tale of two GTPases. Semin Cancer Biol. 54, 29–39 (2019)PubMedCrossRef

15.

N. Minato, K. Kometani, M. Hattori, Regulation of immune responses and hematopoiesis by the Rap1 signal. Adv. Immunol. 93, 229–264 (2007)PubMedCrossRef

16.

J.J. Hamey, M.R. Wilkins, Methylation of elongation factor 1A: where, who, and why?. Trends Biochem Sci. 43(3), 211–223 (2018)PubMedCrossRef

17.

J. Pelletier, N. Sonenberg, The organizing principles of eukaryotic ribosome recruitment. Annu Rev. Biochem 88, 307–335 (2019)PubMedCrossRef

18.

H.J. Lee et al. Immunogenetics of autoimmune thyroid diseases: A comprehensive review. J. Autoimmun. 64, 82–90 (2015)PubMedPubMedCentralCrossRef

19.

P.S. Minhas et al. Macrophage de novo NAD(+) synthesis specifies immune function in aging and inflammation. Nat. Immunol. 20(1), 50–63 (2019)PubMedCrossRef

20.

E.L. Mills et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 167(2), 457–470 e13 (2016)PubMedPubMedCentralCrossRef

21.

S.A. Vardhana et al. Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen. Nat. Immunol. 21(9), 1022–1033 (2020)PubMedPubMedCentralCrossRef

22.

Y. Zhao et al. m(6)A-binding proteins: the emerging crucial performers in epigenetics. J. Hematol. Oncol. 13(1), 35 (2020)PubMedPubMedCentralCrossRef

23.

S. Fang et al. Mechanisms that underly T cell immunity in graves’ orbitopathy. Front Endocrinol. (Lausanne) 12, 648732 (2021)CrossRef

24.

S. Crotty, Do memory CD4 T cells keep their cell-type programming: plasticity versus fate commitment? Complexities of interpretation due to the heterogeneity of memory CD4 T cells, including T follicular helper cells. Cold Spring Harb. Perspect. Biol. 10(3), a032102 (2018) PubMedPubMedCentralCrossRef

25.

S. Sengupta, R.F. Siliciano, Targeting the latent reservoir for HIV-1. Immunity 48(5), 872–895 (2018)PubMedPubMedCentralCrossRef

26.

S. Sureshchandra et al. Phenotypic and epigenetic adaptations of cord blood CD4+ T cells to maternal obesity. Front Immunol. 12, 617592 (2021)PubMedPubMedCentralCrossRef

27.

Z. Wang et al. IP-10 promotes latent HIV infection in resting memory CD4(+) T cells via LIMK-cofilin pathway. Front Immunol. 12, 656663 (2021)PubMedPubMedCentralCrossRef

28.

N. Corcos et al. Oral Fc-coupled preproinsulin achieves systemic and thymic delivery through the neonatal Fc receptor and partially delays autoimmune diabetes. Front Immunol. 12, 616215 (2021)PubMedPubMedCentralCrossRef

29.

T. Liu et al. Human eukaryotic elongation factor 1A forms oligomers through specific cysteine residues. Acta Biochim Biophys. Sin. (Shanghai) 47(12), 1011–1017 (2015)CrossRef

30.

Z. Cai et al. A three-gene signature and clinical outcome in pediatric acute myeloid leukemia. Clin. Transl. Oncol. 23(4), 866–873 (2021)PubMedCrossRef

31.

H.J. Ditzel et al. Cloning and expression of a novel human antibody-antigen pair associated with Felty’s syndrome. Proc. Natl Acad. Sci. USA 97(16), 9234–9239 (2000)PubMedPubMedCentralCrossRef

32.

Q. Feng et al. Etodolac improves collagen induced rheumatoid arthritis in rats by inhibiting synovial inflammation, fibrosis and hyperplasia. Mol. Biomed. 2(1), 33 (2021)PubMedPubMedCentralCrossRef

Title: Identification of two potential immune-related biomarkers of Graves’ disease based on integrated bioinformatics analyses
Authors: Yihan Zhang
Jia Wei
Hong Zhou
Bingxin Li
Ying Chen
Feng Qian
Jingting Liu
Xin Xie
Huanbai Xu
Publication date: 13-08-2022
Publisher: Springer US
Keyword: Biomarkers
Published in: Endocrine / Issue 2/2022
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-022-03156-y

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Identification of two potential immune-related biomarkers of Graves’ disease based on integrated bioinformatics analyses

Abstract

Background

Method

Result

Conclusion

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