Biomarker analysis of systemic sclerosis associated interstitial lung disease based on bioinformatics_West China Medical Journal

Authors：

ZHAO Panpan ¹ , XU Bo ¹ ,  ZHENG Fuzeng ²

1. College of Orthopedics and Traumatology, Henan University of Chinese Medicine, Zhengzhou, Henan 450003, P. R. China;
2. Department of Rheumatology, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan 450003, P. R. China;

Corresponding author：

ZHENG Fuzeng, Email: zhengfuzengyx@126.com

Keywords：

Systemic sclerosis; interstitial lung disease; bioinformatics

DOI：

10.7507/1002-0179.202306192

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To analyze the pathways, biomarkers and diagnostic genes of systemic sclerosis associated interstitial lung disease (SSc-ILD) using bioinformatics. Methods SSc-ILD related gene data sets from April to June 2023 were downloaded from the Gene Expression Omnibus database for differential analysis and enrichment analyses including gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, disease ontology analysis, and gene set enrichment analysis. Least absolute shrinkage and selection operator regression and support vector machine algorithms were applied to screen and take the intersection to get the diagnostic genes and validate the results. Disease-related data were analyzed by immune cell infiltration. Results A total of 178 differential genes were obtained, and enrichment analyses showed that they were related to 5 signaling pathways and associated with 3 diseases. The diagnostic genes screened were TNFAIP3, ID3, and NT5DC2, and immune cell infiltration showed that the diagnostic genes were associated with plasma cells, resting mast cells, activated natural killer cells, macrophage M1 and M2, resting dendritic cells, and activated dendritic cells. Conclusion The screened diagnostic genes and immune cells may be involved in the development of SSc-ILD.

Citation： ZHAO Panpan, XU Bo, ZHENG Fuzeng. Biomarker analysis of systemic sclerosis associated interstitial lung disease based on bioinformatics. West China Medical Journal, 2023, 38(9): 1347-1353. doi: 10.7507/1002-0179.202306192 Copy

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2.	Akter T, Silver RM, Bogatkevich GS. Recent advances in understanding the pathogenesis of scleroderma-interstitial lung disease. Curr Rheumatol Rep, 2014, 16(4): 411.
3.	吴晓, 王庆文. 系统性硬化病相关肺部疾病的诊治进展. 中华肺部疾病杂志(电子版), 2020, 13(2): 282-285.
4.	刘孟国, 李明, 傅雯雯. 系统性硬化症的生物制剂治疗新进展. 医学综述, 2021, 27(9): 1765-1769.
5.	Li M, Krishnaveni MS, Li C, et al. Epithelium-specific deletion of TGF-β receptor type II protects mice from bleomycin-induced pulmonary fibrosis. J Clin Invest, 2011, 121(1): 277-287.
6.	陈相, 李耀浙, 傅扬扬, 等. 1990-2019 年中国间质性肺疾病和肺结节病的疾病负担分析. 疾病监测, 2023, 38(4): 473-480.
7.	Jang HJ, Woo A, Kim SY, et al. Characteristics and risk factors of mortality in patients with systemic sclerosis-associated interstitial lung disease. Ann Med, 2023, 55(1): 663-671.
8.	任亚飞, 蒋亚男, 谢璠, 等. 系统性硬化症相关间质性肺疾病的机制研究. 实用医学杂志, 2018, 34(19): 3307-3309.
9.	Grossman C, Dovrish Z, Shoenfeld Y, et al. Do infections facilitate the emergence of systemic sclerosis?. Autoimmun Rev, 2011, 10(5): 244-247.
10.	Sawadpanich K, Promasen P, Mairiang P, et al. Incidence and predictors of an abnormal liver function test among 674 systemic sclerosis patients: a cohort study. Open Access Rheumatol, 2023, 15: 81-92.
11.	Hashimoto A, Arinuma Y, Nagai T, et al. Incidence and the risk factor of malignancy in Japanese patients with systemic sclerosis. Intern Med, 2012, 51(13): 1683-1688.
12.	Moon KW, Lee SS, Lee YJ, et al. Clinical and laboratory characteristics and mortality in Korean patients with systemic sclerosis: a nationwide multicenter retrospective cohort study. J Rheumatol, 2018, 45(9): 1281-1288.
13.	陶志清, 赵铖. TNF-α 与系统性硬化病关系的研究进展. 中国免疫学杂志, 2021, 37(15): 1902-1907.
14.	Dieudé P, Guedj M, Wipff J, et al. NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis. Ann Rheum Dis, 2011, 70(4): 668-674.
15.	Li Z, Guo J, Bi L. Role of the NLRP3 inflammasome in autoimmune diseases. Biomed Pharmacother, 2020, 130: 110542.
16.	O’Reilly S. Toll-like receptor triggering in systemic sclerosis: time to target. Rheumatology (Oxford), 2023, 62(SI): SI12-SI19.
17.	李娜, 王健健, 张帅, 等. TNFAIP3 基因多态性与自身免疫性疾病相关性的研究进展. 中国免疫学杂志, 2014, 30(9): 1278-1281.
18.	Wang W, Bale S, Wei J, et al. Fibroblast A20 governs fibrosis susceptibility and its repression by DREAM promotes fibrosis in multiple organs. Nat Commun, 2022, 13(1): 6358.
19.	Mody AA, Wordinger RJ, Clark AF. Role of ID proteins in BMP4 inhibition of profibrotic effects of TGF-β2 in human TM cells. Invest Ophthalmol Vis Sci, 2017, 58(2): 849-859.
20.	Qiaolongbatu X, Zhao W, Huang X, et al. The therapeutic mechanism of Schisandrol A and its metabolites on pulmonary fibrosis based on plasma metabonomics and network analysis. Drug Des Devel Ther, 2023, 17: 477-496.
21.	Moita MR, Silva MM, Diniz C, et al. Transcriptome and proteome profiling of activated cardiac fibroblasts supports target prioritization in cardiac fibrosis. Front Cardiovasc Med, 2022, 9: 1015473.
22.	Carvalheiro T, Zimmermann M, Radstake TRDJ, et al. Novel insights into dendritic cells in the pathogenesis of systemic sclerosis. Clin Exp Immunol, 2020, 201(1): 25-33.
23.	Brown M, O’Reilly S. The immunopathogenesis of fibrosis in systemic sclerosis. Clin Exp Immunol, 2019, 195(3): 310-321.
24.	Frantz C, Pezet S, Avouac J, et al. Soluble CD163 as a potential biomarker in systemic sclerosis. Dis Markers, 2018, 2018: 8509583.
25.	Hügle T. Beyond allergy: the role of mast cells in fibrosis. Swiss Med Wkly, 2014, 144: w13999.
26.	Padilla CM, Valenzi E, Tabib T, et al. Increased CD8⁺ tissue resident memory T cells, regulatory T cells, and activated natural killer cells in systemic sclerosis lungs. Rheumatology (Oxford), 2023: kead273.

1. 李国铨, 郭峰, 王敏, 等. 系统性硬化症并间质性肺疾病与外周血 T 细胞亚群的相关性研究. 海南医学, 2021, 32(14): 1789-1793.
2. Akter T, Silver RM, Bogatkevich GS. Recent advances in understanding the pathogenesis of scleroderma-interstitial lung disease. Curr Rheumatol Rep, 2014, 16(4): 411.
3. 吴晓, 王庆文. 系统性硬化病相关肺部疾病的诊治进展. 中华肺部疾病杂志(电子版), 2020, 13(2): 282-285.
4. 刘孟国, 李明, 傅雯雯. 系统性硬化症的生物制剂治疗新进展. 医学综述, 2021, 27(9): 1765-1769.
5. Li M, Krishnaveni MS, Li C, et al. Epithelium-specific deletion of TGF-β receptor type II protects mice from bleomycin-induced pulmonary fibrosis. J Clin Invest, 2011, 121(1): 277-287.
6. 陈相, 李耀浙, 傅扬扬, 等. 1990-2019 年中国间质性肺疾病和肺结节病的疾病负担分析. 疾病监测, 2023, 38(4): 473-480.
7. Jang HJ, Woo A, Kim SY, et al. Characteristics and risk factors of mortality in patients with systemic sclerosis-associated interstitial lung disease. Ann Med, 2023, 55(1): 663-671.
8. 任亚飞, 蒋亚男, 谢璠, 等. 系统性硬化症相关间质性肺疾病的机制研究. 实用医学杂志, 2018, 34(19): 3307-3309.
9. Grossman C, Dovrish Z, Shoenfeld Y, et al. Do infections facilitate the emergence of systemic sclerosis?. Autoimmun Rev, 2011, 10(5): 244-247.
10. Sawadpanich K, Promasen P, Mairiang P, et al. Incidence and predictors of an abnormal liver function test among 674 systemic sclerosis patients: a cohort study. Open Access Rheumatol, 2023, 15: 81-92.
11. Hashimoto A, Arinuma Y, Nagai T, et al. Incidence and the risk factor of malignancy in Japanese patients with systemic sclerosis. Intern Med, 2012, 51(13): 1683-1688.
12. Moon KW, Lee SS, Lee YJ, et al. Clinical and laboratory characteristics and mortality in Korean patients with systemic sclerosis: a nationwide multicenter retrospective cohort study. J Rheumatol, 2018, 45(9): 1281-1288.
13. 陶志清, 赵铖. TNF-α 与系统性硬化病关系的研究进展. 中国免疫学杂志, 2021, 37(15): 1902-1907.
14. Dieudé P, Guedj M, Wipff J, et al. NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis. Ann Rheum Dis, 2011, 70(4): 668-674.
15. Li Z, Guo J, Bi L. Role of the NLRP3 inflammasome in autoimmune diseases. Biomed Pharmacother, 2020, 130: 110542.
16. O’Reilly S. Toll-like receptor triggering in systemic sclerosis: time to target. Rheumatology (Oxford), 2023, 62(SI): SI12-SI19.
17. 李娜, 王健健, 张帅, 等. TNFAIP3 基因多态性与自身免疫性疾病相关性的研究进展. 中国免疫学杂志, 2014, 30(9): 1278-1281.
18. Wang W, Bale S, Wei J, et al. Fibroblast A20 governs fibrosis susceptibility and its repression by DREAM promotes fibrosis in multiple organs. Nat Commun, 2022, 13(1): 6358.
19. Mody AA, Wordinger RJ, Clark AF. Role of ID proteins in BMP4 inhibition of profibrotic effects of TGF-β2 in human TM cells. Invest Ophthalmol Vis Sci, 2017, 58(2): 849-859.
20. Qiaolongbatu X, Zhao W, Huang X, et al. The therapeutic mechanism of Schisandrol A and its metabolites on pulmonary fibrosis based on plasma metabonomics and network analysis. Drug Des Devel Ther, 2023, 17: 477-496.
21. Moita MR, Silva MM, Diniz C, et al. Transcriptome and proteome profiling of activated cardiac fibroblasts supports target prioritization in cardiac fibrosis. Front Cardiovasc Med, 2022, 9: 1015473.
22. Carvalheiro T, Zimmermann M, Radstake TRDJ, et al. Novel insights into dendritic cells in the pathogenesis of systemic sclerosis. Clin Exp Immunol, 2020, 201(1): 25-33.
23. Brown M, O’Reilly S. The immunopathogenesis of fibrosis in systemic sclerosis. Clin Exp Immunol, 2019, 195(3): 310-321.
24. Frantz C, Pezet S, Avouac J, et al. Soluble CD163 as a potential biomarker in systemic sclerosis. Dis Markers, 2018, 2018: 8509583.
25. Hügle T. Beyond allergy: the role of mast cells in fibrosis. Swiss Med Wkly, 2014, 144: w13999.
26. Padilla CM, Valenzi E, Tabib T, et al. Increased CD8⁺ tissue resident memory T cells, regulatory T cells, and activated natural killer cells in systemic sclerosis lungs. Rheumatology (Oxford), 2023: kead273.

West China Medical Journal

Biomarker analysis of systemic sclerosis associated interstitial lung disease based on bioinformatics

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