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Study on immune biomarker of gout and screening of related target Chinese medicine based on the xCell algorithm

Published on Jul. 02, 2024Total Views: 1033 times Total Downloads: 240 times Download Mobile

Author: LI Lingqin 1 ZHOU Ruijiao 2 ZHANG Yanni 3 YUAN Xinzhu 4

Affiliation: 1. Department of Rheumatology and Immunology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China 2. Department of Neurology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China 3. Department of Nephrology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China 4. Department of Nephrology, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong 637003, Sichuan Province, China

Keywords: Gout Chinese medicine Bioinformatics Immune markers Arthritis Metabolic syndrome Monosodium urate Gene microarray

DOI: 10.12173/j.issn.1008-049X.202311291

Reference: LI Lingqin, ZHOU Ruijiao, ZHANG Yanni, YUAN Xinzhu.Study on immune biomarker of gout and screening of related target Chinese medicine based on the xCell algorithm[J].Zhongguo Yaoshi Zazhi,2024, 27(6):1007-1018.DOI: 10.12173/j.issn.1008-049X.202311291.[Article in Chinese]

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Abstract

Objective  To study the key genes and immune biomarkers of gout and to explore potential target Chinese medicine, which can provide new directions for the clinical treatment of gout.

Methods  The gout microarray dataset was downloaded from the GEO database, the differential genes were screened using R software, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on these differential genes. The STRING database was applied to analyze the protein interaction network of the differential genes, and the Cytoscape was used to screen the key genes. The protein expression levels of key genes were validated using the ELISA method. Furthermore, the xCell was used to estimate the relative expression and correlation of immune cells in gout. Finally, the significantly enriched immune-related biological processes and key target genes of Chinese medicine were predicted by Coremine Medical database.

Results  A total of 852 differential gout genes were screened. GO enrichment analysis was mainly enriched in the leukocyte chemotaxis, interleukin-2 production, and regulation of vasculature development; KEGG pathway was mainly enriched in IL-17 signaling pathway, Chemokine signaling pathway, and TNF signaling pathway. Ten key genes, including TNF, IL-6, IL-1β, CXCL8, FOS, and VEGFA etc, were selected. The experimental validation showed that the protein expression levels of key genes were consistent with the expression trends of the chip data. Immune infiltration showed that monocytes, memory B cells, CD8+ T-cells and IDC were closely associated with gout. Herbal predictions had identified Ginseng, Panax notoginseng, Scutellaria, Baicalensis, Saururus chinensis, and Salvia miltiorrhiza as potential drugs for the treatment of gout.

Conclusion  This study identified possible key genes and immune mechanisms contributing to the pathogenesis of gout, and discovered potential targetable traditional Chinese medicine. These key genes and herbs are expected to offer new insights and methods for the treatment of gout.

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1.Yang QB, Li LQ, Zhang QB, et al. microRNA-223 deficiency exacerbates acute inflammatory response to monosodium urate crystals by targeting nlrp3[J]. J Inflamm Res, 2021, 14: 1845-1858. DOI: 10.2147/JIR.S307796.

2.Singh JA, Gaffo A. Gout epidemiology and comorbidities[J]. Semin Arthritis Rheum, 2020, 50(3S): S11-S16. DOI: 10.1016/j.semarthrit.2020.04.008.

3.Ashiq K, Bajwa MA, Tanveer S, et al. A comprehensive review on gout: the epidemiological trends, pathophysiology, clinical presentation, diagnosis and treatment[J]. J Pak Med Assoc, 2021, 71(4): 1234-1238. DOI: 10.47391/JPMA.313.

4.Dehlin M, Jacobsson L, Roddy E. Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors[J]. Nat Rev Rheumatol, 2020, 16(7): 380-390. DOI: 10.1038/s41584-020-0441-1.

5.Chen F, Zhang X, Chen Y, et al. Construction of lncRNA-miRNA-mRNA network based on ceRNA mechanism reveals the function of lncRNA in the pathogenesis of gout[J]. J Clin Lab Anal, 2022, 36(6): e24451. DOI: 10.1002/jcla.24451.

6.Liu W, Wu YH, Xue B, et al. Effect of integrated traditional Chinese and western medicine on gout[J]. J Tradit Chin Med, 2021, 41(5): 806-816. DOI: 10.19852/j.cnki.jtcm.20210702.001.

7.So AK, Martinon F. Inflammation in gout: mechanisms and therapeutic targets[J]. Nat Rev Rheumatol, 2017, 13(11): 639-647. DOI: 10.1038/nrrheum.2017.155.

8.Aran D, Hu Z, Butte AJ. xCell: digitally portraying the tissue cellular heterogeneity landscape[J]. Genome Biol, 2017, 18(1): 220. DOI: 10.1186/s13059-017-1349-1.

9.Frazaei MH, Nouri R, Nezhad RA, et al. A review of medicinal plants and phytochemicals for the management of gout[J]. Curr Rheumatol Rev, 2024, 20(3): 223-240. DOI: 10.2174/0115733971268037230920072503.

10.Qing YF, Zheng JX, Tang YP, et al. LncRNAs Landscape in the patients of primary gout by microarray analysis[J]. PLoS One, 2021, 16(2): e0232918. DOI: 10.1371/journal.pone.0232918.

11.赵盼盼, 许博, 郑福增. 基于生物信息学的系统性硬化症相关间质性肺病生物标志物分析[J]. 华西医学, 2023, 38(9): 1347-1353. [Zhao PP, Xu B, Zheng FZ, et al. Biomarker analysis of systemic sclerosis associated interstitial lung disease based on bioinformatics[J]. West China Medical Journal, 2023, 38(9): 1347-1353.] DOI: 10.7507/1002-0179.202306192.

12.Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible[J]. Nucleic Acids Res, 2017, 45(D1): D362-D368. DOI: 10.1093/nar/gkw937.

13.谭宗标, 刘传, 曾愫琦, 等. 炎症性肠病与类风湿性关节炎[J]. 医学新知, 2022, 32(5): 365-369. [Tan ZB, Liu C, Zeng SQ, et al. Inflammatory bowel disease and rheumatoid arthritis[J]. Yixue Xinzhi Zazhi, 2022, 32(5): 365-369.] DOI: 10.12173/j.issn.1004-5511.202207026.

14.姜美华, 韩志武, 徐友平, 等. 双醋瑞因联合不同剂量依托考昔治疗急性重度痛风性关节炎的回顾性临床观察[J]. 中国药师, 2022, 25(3): 486-489. [Jiang MH, Han ZW, Xu YP, et al. Retrospective clinical observation of diacerein combined with different doses of etoricoxib in the treatment of acute severe gouty arthritis[J]. China Pharmacist, 2022, 25(3): 486-489.] DOI: 10.19962/j.cnki.issn1008-049X.2022.03.019.

15.Zhang QB, Zhu D, Dai F, et al. MicroRNA-223 suppresses IL-1beta and TNF-alpha production in gouty inflammation by targeting the NLRP3 inflammasome[J]. Front Pharmacol, 2021, 12: 637415. DOI: 10.3389/fphar.2021.637415.

16.Chang SJ, Tsai PC, Chen CJ, et al. The polymorphism -863C/A in tumour necrosis factor-alpha gene contributes an independent association to gout[J]. Rheumatology (Oxford), 2007, 46(11): 1662-1666. DOI: 10.1093/rheumatology/kem235.

17.Amaral FA, Bastos LF, Oliveira TH, et al. Transmembrane TNF-α is sufficient for articular inflammation and hypernociception in a mouse model of gout[J]. Eur J Immunol, 2016, 46(1): 204-211. DOI: 10.1002/eji.201545798.

18.Zhang Y, Pan R, Xu Y, et al. Treatment of refractory gout with TNF-α antagonist etanercept combined with febuxostat[J]. Ann Palliat Med, 2020, 9(6): 4332-4338. DOI: 10.21037/apm-20-2072.

19.Hirano T. IL-6 in inflammation, autoimmunity and cancer[J]. Int Immunol, 2021, 33(3): 127-148. DOI: 10.1093/intimm/dxaa078.

20.Liao Y, Ren Y, Luo X, et al. Interleukin-6 signaling mediates cartilage degradation and pain in posttraumatic osteoarthritis in a sex-specific manner[J]. Sci Signal, 2022, 15(744): eabn7082. DOI: 10.1126/scisignal.abn7082.

21.Cavalcanti NG, Marques CD, Lins ELTU, et al. Cytokine profile in gout: inflammation driven by IL-6 and IL-18[J]. Immunol Invest, 2016, 45(5): 383-395. DOI: 10.3109/ 08820139.2016.1153651.

22.Pandolfi F, Franza L, Carusi V, et al. Interleukin-6 in rheumatoid arthritis[J]. Int J Mol Sci, 2020, 21(15): 5238. DOI: 10.3390/ijms21155238.

23.Nepal D, Gazeley D. Role of IL-6 and IL-6 targeted therapy in systemic lupus erythematosus[J]. Rheumatology (Oxford), 2023, 62(12): 3804-3810. DOI: 10.1093/rheumatology/kead416.

24.Grebenciucova E, Vanhaerents S. Interleukin 6: at the interface of human health and disease[J]. Front Immunol, 2023, 14: 1255533. DOI: 10.3389/fimmu.2023.1255533.

25.Sil P, Wicklum H, Surell C, et al. Macrophage-derived IL-1beta enhances monosodium urate crystal-triggered NET formation[J]. Inflamm Res, 2017, 66(3): 227-237. DOI: 10.1007/s00011-016-1008-0.

26.Schett G, Dayer JM, Manger B. Interleukin-1 function and role in rheumatic disease[J]. Nat Rev Rheumatol, 2016, 12(1): 14-24. DOI: 10.1038/nrrheum.2016.166.

27.Elsayed S, Jay GD, Cabezas R, et al. Recombinant human proteoglycan 4 regulates phagocytic activation of monocytes and reduces IL-1beta secretion by urate crystal stimulated gout PBMCs[J]. Front Immunol, 2021, 12: 771677. DOI: 10.3389/fimmu.2021.771677.

28.Kienhorst LB, van Lochem E, Kievit W, et al. Gout is a chronic inflammatory disease in which high levels of Interleukin-8 (CXCL8), myeloid-related protein 8/ myeloid-related protein 14 complex, and an altered proteome are associated with diabetes mellitus and cardiovascular disease[J]. Arthritis Rheumatol, 2015, 67(12): 3303-3313. DOI: 10.1002/art.39318.

29.Kienhorst L, Janssens H, Radstake T, et al. A pilot study of CXCL8 levels in crystal proven gout patients during allopurinol treatment and their association with cardiovascular disease[J]. Joint Bone Spine, 2017, 84(6): 709-713. DOI: 10.1016/j.jbspin.2016.10.013.

30.Qing YF, Zhang QB, Zhou JG. Innate immunity functional gene polymorphisms and gout susceptibility[J]. Gene, 2013, 524(2): 412-414. DOI: 10.1016/j.gene.2013.04.039.

31.Cabau G, Crisan TO, Kluck V, et al. Urate-induced immune programming: consequences for gouty arthritis and hyperuricemia[J]. Immunol Rev, 2020, 294(1): 92-105. DOI: 10.1111/imr.12833.

32.Gazeau P, Alegria GC, Devauchelle-Pensec V, et al. Memory B cells and response to abatacept in rheumatoid arthritis[J]. Clin Rev Allergy Immunol, 2017, 53(2): 166-176. DOI: 10.1007/s12016-017-8603-x.

33.Barcelos F, Martins C, Papoila A, et al. Association between memory B-cells and clinical and immunological features of primary sjogren's syndrome and sicca patients[J]. Rheumatol Int, 2018, 38(6): 1063-1073. DOI: 10.1007/s00296-018-4018-0.

34.Hu Z, Jiao Q, Ding J, et al. Berberine induces dendritic cell apoptosis and has therapeutic potential for rheumatoid arthritis[J]. Arthritis Rheum, 2011, 63(4): 949-959. DOI: 10.1002/art.30202.

35.Hu F, Zhang W, Shi L, et al. Impaired CD27+IgD+ B cells with altered gene signature in rheumatoid arthritis[J]. Front Immunol, 2018, 9: 626. DOI: 10.3389/fimmu.2018.00626.

36.Agrawal S, Gupta S. TLR1/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and memory B cell subsets to produce cytokines, chemokines, and hematopoietic growth factors[J]. J Clin Immunol, 2011, 31(1): 89-98. DOI: 10.1007/s10875-010-9456-8.

37.Weller S, Braun MC, Tan BK, et al. Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire[J]. Blood, 2004, 104(12): 3647-3654. DOI: 10.1182/blood-2004-01-0346.

38.Castleman MJ, Santos AL, Lesteberg KE, et al. Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection[J]. Front Immunol, 2023, 14: 1213344. DOI: 10.3389/fimmu. 2023.1213344.

39.Garcia-Maturano JS, Torres-Ordaz DE, Mosqueda-Gutierrez M, et al. Gout during the SARS-CoV-2 pandemic: increased flares, urate levels and functional improvement[J]. Clin Rheumatol, 2022, 41(3): 811-818. DOI: 10.1007/s10067-021-05994-z.

40.刘明岭, 陈靖雯, 何家颖, 等. 痛风急性发作期中医证候特征的临床研究[J]. 广州中医药大学学报, 2022, 39(7): 1482-1486. [Liu ML, Chen JW, He JY, et al. Clinical study on the characteristics of traditional Chinese medicine syndromes in gout patients with acute attack[J]. Journal of Guangzhou University of Traditional Chinese Medicine, 2022, 39(7): 1482-1486.] DOI: 10.13359/j.cnki.gzxbtcm.2022.07.004.

41.Xiao N, Chen H, He SY, et al. Evaluating the efficacy and adverse effects of clearing heat and removing dampness method of traditional Chinese medicine by comparison with western medicine in patients with gout[J]. Evid Based Complement Alternat Med, 2018, 2018: 8591349. DOI: 10.1155/2018/8591349.

42.Lee D, Lee J, Vu-Huynh KL, et al. Protective effect of panaxynol isolated from panax vietnamensis against cisplatin-induced renal damage: in vitro and in vivo studies[J]. Biomolecules, 2019, 9(12): 890. DOI: 10.3390/biom9120890.

43.Zhang Y, Su H, Zhang J, et al. The effects of ginsenosides and anserine on the up-regulation of renal aquaporins 1-4 in hyperuricemic mice[J]. Am J Chin Med, 2019, 47(5): 1133-1147. DOI: 10.1142/S0192415X19500587.

44.Sung YY, Yuk HJ, Kim DS. Saengmaeksan, a traditional herbal formulation consisting of panax ginseng, ameliorates hyperuricemia by inhibiting xanthine oxidase activity and enhancing urate excretion in rats[J]. J Ginseng Res, 2021, 45(5): 565-574. DOI: 10.1016/j.jgr.2021.01.001.

45.李志远, 刘屹, 李哲媛, 等. 2020年云南省三七中3种皂苷含量测定能力验证结果评价[J]. 中国药师, 2022, 25(6): 1126-1129. [Li ZY, Liu Y, Li ZY, et al. Evaluation on the results of proficiency test for the determination of three saponins in panax notoginseng in yunnan province in 2020[J]. China Pharmacist, 2022, 25(6): 1126-1129.] DOI: 10.19962/j.cnki.issn1008-049X.2022.06.040.

46.Su P, Du S, Li H, et al. Notoginsenoside R1 inhibits oxidized low-density lipoprotein induced inflammatory cytokines production in human endothelial EA.hy926 cells[J]. Eur J Pharmacol, 2016, 770: 9-15. DOI: 10.1016/j.ejphar.2015.11.040.

47.张福康, 杨妍华, 陆再华. 三七总皂苷对以尿酸钠诱导血管内皮细胞凋亡的影响[J]. 中华中医药学刊, 2012, 30(8): 1843-1845, 1925. [Zhang FK,Yang YH, Lu ZH. Effect of panax notoginsenosides on vascular endothelial cells apoptosis induced by sodium urate(MSU)[J]. Chinese Archives of Traditional Chinese Medicine, 2012, 30(8): 1843-1845, 1925.] DOI: 10.13193/j.archtcm.2012.08.149.zhangfk.054.

48.曹塬, 刘杰. 土三七提取物对尿酸钠诱导的大鼠急性痛风性关节炎的缓解作用[J]. 食品工业科技, 2019, 40(13): 253-256, 263. [Cao Y, Liu J. Alleviating effect of garcinia extract on acute gouty arthritis induced by sodium uric acid in rats[J]. Science and Technology of Food Industry, 2019, 40(13): 253-256, 263.] DOI: 10.13386/j.issn1002-0306.2019.13.042.

49.Li D, Li S, Zhao J. Screening of xanthine oxidase inhibitors in complex mixtures using online HPLC coupled with postcolumn fluorescence-based biochemical detection[J]. J Sep Sci, 2014, 37(4): 338-344. DOI: 10.1002/jssc. 201301207.

50.Jung SM, Schumacher HR, Kim H, et al. Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D2 levels[J]. Arthritis Res Ther, 2007, 9(4): R64. DOI: 10.1186/ar2222.

51.夏鸿杰, 赵峥嵘, 郭静, 等. 中医相关证据质量及推荐意见分级体系的系统评价[J]. 中国循证医学杂志, 2022, 22(2): 187-195. [Xia HJ, Zhao ZR, Guo J, et al. Traditional Chinese medicine related grading criteria for quality of evidence and strength of recommendations: a systematic review[J]. Chinese Journal of Evidence-Based Medicine, 2022, 22(2): 187-195.] DOI: 10.7507/1672-2531.202110021.

52.郝蕊, 郭凤, 蒋洁, 等. 丹参-黄芪调节自噬防治糖尿病心肌病的lncRNA-miRNA-mRNA转录网络研究 [J]. 药物流行病学杂志, 2023, 32(10): 1113-1126. [Hao R, Guo F, Jiang J, et al. The lncRNA-mi-RNA-mRNA transcription network of the salvia miltiorrhixa bge-hedysarum multijugum maxim in preventing and treating diabetic cardiomyopathy by regulating autophagy[J]. Chinese Journal of Pharmacoepidemiology, 2023, 32(10): 1113-1126.] DOI: 10.19960/j.issn.1005-0698. 202310005.

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