Bioinformatic analysis of differentially expressed genes of primary Sjögren's syndrome

doi:10.3969/j.issn.1004-583X.2024.09.004

Abstract

Abstract:

Objective To screen for differentially expressed genes (DEGs) associated with primary Sjögren's syndrome(pSS) by bioinformatics and to explore its underlying pathogenesis. Methods Gene expression profiles were downloaded from the GEO database, and DEGs were obtained by integrating the datasets. Furthermore, we explored DEGs’ potential function by GO and KEGG enrichment analysis. Finally, we screened the hub genes of pSS by PPI network analysis. Results A total of 29 DEGs(27 up-regulated and 2 down-regulated) were identified, and the GO enrichment results showed that these genes are involved in lymphocyte and monocyte differentiation and proliferation, T cell activation, positive regulation of cell-cell adhesion, and chemokine-related molecular functions. KEGG analysis mainly involves chemokine signaling pathways, hematopoietic cell regulatory signaling pathways, B cell receptor signaling, viral protein-cytokine and receptor interaction pathways. Five hub genes, including MX1, SELL, IFIT1, IFI44L and SAMD9L were screened from the PPI network.Conclusion The MX1, SELL, IFIT1, IFI44L, and SAMD9L genes were identified and may be involved in pSS pathogenesis.

Key words: primary Sjögren’s syndrome, bioinformatics, DEGs

CLC Number:

R593.2

Wang Yun, Wang Dandan. Bioinformatic analysis of differentially expressed genes of primary Sjögren's syndrome[J]. Clinical Focus, 2024, 39(9): 792-797.

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2024.09.004

https://huicui.hebmu.edu.cn/EN/Y2024/V39/I9/792

Figures/Tables 4

References 34

[1]	Nocturne G, Virone A, Ng WF, et al. Rheumatoid factor and disease activity are independent predictors of lymphoma in primary Sjögren's syndrome[J]. Arthritis Rheumatol, 2016, 68(4):977-985.
[2]	中华医学会风湿病学分会. 干燥综合征诊断及治疗指南[J]. 中华风湿病学杂志, 2010, 14(11):766-768.
[3]	Greenwell-Wild T, Moutsopoulos NM, Gliozzi M, et al. Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: Macrophage harbingers of disease severity[J]. Arthritis Rheum, 2011, 63(10):3103-3115.
[4]	Horvath S, Nazmul-Hossain AN, Pollard RP, et al. Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model[J]. Arthritis Res Ther, 2012, 14(6):R238.
[5]	Leek JT, Johnson WE, Parker HS, et al. The sva package for removing batch effects and other unwanted variation in high-throughput experiments[J]. Bioinformatics, 2012, 28(6):882-883. doi: 10.1093/bioinformatics/bts034 pmid: 22257669
[6]	Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies[J]. Nucleic Acids Res, 2015, 43(7):e47.
[7]	Yu G, Wang LG, Han Y, et al. ClusterProfiler: An R package for comparing biological themes among gene clusters[J]. OMICS, 2012, 16(5):284-287. doi: 10.1089/omi.2011.0118 pmid: 22455463
[8]	von Mering C, Huynen M, Jaeggi D, et al. STRING: A database of predicted functional associations between proteins[J]. Nucleic Acids Res, 2003, 31(1):258-261. doi: 10.1093/nar/gkg034 pmid: 12519996
[9]	Shannon P, Markiel A, Ozier O, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks[J]. Genome Res, 2003, 13(11):2498-2504. doi: 10.1101/gr.1239303 pmid: 14597658
[10]	Chin CH, Chen SH, Wu HH, et al. CytoHubba: Identifying hub objects and sub-networks from complex interactome[J]. BMC Syst Biol, 2014, 8:S11.
[11]	Kang HI, Fei HM, Saito I, et al. Comparison of HLA class II genes in Caucasoid, Chinese, and Japanese patients with primary Sjögren's syndrome[J]. J Immunol, 1993, 150:3615-3623. pmid: 8468491
[12]	Ishimaru N, Arakaki R, Yoshida S, et al. Expression of the retinoblastoma protein RbAp48 in exocrine glands leads to Sjögren's syndrome-like autoimmune exocrinopathy[J]. J Exp Med, 2008, 205(12):2915-2927.
[13]	Saito I, Servenius B, Compton T, et al. Detection of epstein-Barr virus DNA by polymerase chain reaction in blood and tissue biopsies from patients with Sjogren's syndrome[J]. J Exp Med, 1989, 169(6):2191-2198. doi: 10.1084/jem.169.6.2191 pmid: 2543732
[14]	Moriyama M, Hayashida JN, Toyoshima T, et al. Cytokine/chemokine profiles contribute to understanding the pathogenesis and diagnosis of primary Sjögren's syndrome[J]. Clin Exp Immunol, 2012, 169(1):17-26. doi: 10.1111/j.1365-2249.2012.04587.x pmid: 22670774
[15]	McArthur C, Wang Y, Veno P, et al. Intracellular trafficking and surface expression of SS-A (Ro), SS-B (La), poly(ADP-ribose) polymerase and alpha-fodrin autoantigens during apoptosis in human salivary gland cells induced by tumour necrosis factor-alpha[J]. Arch Oral Biol, 2002, 47(6):443-448. doi: 10.1016/s0003-9969(02)00025-0 pmid: 12102760
[16]	Naito Y, Matsumoto I, Wakamatsu E, et al. Altered peptide ligands regulate muscarinic acetylcholine receptor reactive T cells of patients with Sjögren's syndrome[J]. Ann Rheum Dis, 2006, 65(2):269-271. pmid: 16410534
[17]	Kong L, Ogawa N, Nakabayashi T, et al. Fas and fas ligand expression in the salivary glands of patients with primary Sjögren's syndrome[J]. Arthritis Rheum, 1997, 40(1):87-97.
[18]	Nakamura H, Koji T, Tominaga M, et al. Apoptosis in labial salivary glands from Sjögren's syndrome (SS) patients: Comparison with human T lymphotropic virus-I (HTLV-I)-seronegative and -seropositive SS patients[J]. Clin Exp Immunol, 1998, 114(1):106-112. pmid: 9764611
[19]	Nakamura H, Kawakami A, Izumi M, et al. Detection of the soluble form of Fas ligand (sFasL) and sFas in the saliva from patients with Sjögren's syndrome[J]. Clin Exp Rheumatol, 2005, 23(6):915. pmid: 16396719
[20]	Tsubota K, Saito I, Miyasaka N. Granzyme A and perforin expressed in the lacrimal glands of patients with Sjögren's syndrome[J]. Am J Ophthalmol, 1994, 117(1):120-121. pmid: 7904795
[21]	Fujihara T, Fujita H, Tsubota K, et al. Preferential localization of CD8+ alpha E beta 7+ T cells around acinar epithelial cells with apoptosis in patients with Sjögren's syndrome[J]. J Immunol, 1999, 163(4):2226-2235. pmid: 10438965
[22]	Carsons SE, Vivino FB, Parke A, et al. Treatment guidelines for rheumatologic manifestations of Sjögren's syndrome: Use of biologic agents, management of fatigue, and inflammatory musculoskeletal Pain[J]. Arthritis Care Res (Hoboken), 2017, 69(4):517-527. doi: 10.1002/acr.22968 pmid: 27390247
[23]	Fensterl V, Sen GC. Interferon-induced Ifit proteins: Their role in viral pathogenesis[J]. J Virol, 2015, 89(5):2462-2468. doi: 10.1128/JVI.02744-14 pmid: 25428874
[24]	Jiang H, Tsang L, Wang H, et al. IFI44L as a forward regulator enhancing host antituberculosis responses[J]. J Immunol Res, 2021, 2021:5599408.
[25]	Haller O, Kochs G. Human MxA protein: An interferon-induced dynamin-like GTPase with broad antiviral activity[J]. J Interferon Cytokine Res, 2011, 31(1):79-87.
[26]	Imgenberg-Kreuz J, Sandling JK, Almlöf JC, et al. Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes[J]. Ann Rheum Dis, 2016, 75(11):2029-2036. doi: 10.1136/annrheumdis-2015-208659 pmid: 26857698
[27]	Bodewes ILA, Versnel MA. Interferon activation in primary Sjögren's syndrome: Recent insights and future perspective as novel treatment target[J]. Expert Rev Clin Immunol, 2018, 14(10):817-829.
[28]	Jhamnani RD, Rosenzweig SD. An update on gain-of-function mutations in primary immunodeficiency diseases[J]. Curr Opin Allergy Clin Immunol, 2017, 17(6):391-397.
[29]	Sahoo SS, Pastor VB, Goodings C, et al. Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes[J]. Nat Med, 2021, 27(10):1806-1817. doi: 10.1038/s41591-021-01511-6 pmid: 34621053
[30]	Allenspach EJ, Soveg F, Finn LS, et al. Germline SAMD9L truncation variants trigger global translational repression[J]. J Exp Med, 2021, 218(5):e20201195.
[31]	Wedepohl S, Beceren-Braun F, Riese S, et al. L-selectin--a dynamic regulator of leukocyte migration[J]. Eur J Cell Biol, 2012, 91(4):257-264. doi: 10.1016/j.ejcb.2011.02.007 pmid: 21546114
[32]	Sarraj B, Ludányi K, Glant TT, et al. Expression of CD44 and L-selectin in the innate immune system is required for severe joint inflammation in the proteoglycan-induced murine model of rheumatoid arthritis[J]. J Immunol, 2006, 177(3):1932-1940. pmid: 16849507
[33]	Kabeerdoss J, Sandhya P, Mandal SK, et al. High salivary soluble L-selectin and interleukin-7 levels in Asian Indian patients with primary Sjögren's syndrome[J]. Clin Rheumatol, 2016, 35(12):3063-3067. pmid: 27620619
[34]	Mikulowska-Mennis A, Xu B, Berberian JM, et al. Lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule-1/alpha(4)beta(1) integrin, peripheral node addressin/l-selectin, and lymphocyte function-associated antigen-1 adhesion pathways[J]. Am J Pathol, 2001, 159(2):671-681. pmid: 11485925

分类	ID	功能	P值	基因数目
GO-BP	GO:0030098	淋巴细胞分化	1.00E-05	6
	GO:0042100	B细胞增殖	1.01E-05	4
	GO:0045621	淋巴细胞分化的正向调节	1.22E-05	4
	GO:1903131	单核细胞分化	2.10E-05	6
	GO:1990266	中性粒细胞迁移	2.30E-05	4
	GO:0022409	细胞-细胞黏附的正向调节	3.93E-05	5
	GO:0046651	淋巴细胞增殖	4.20E-05	5
	GO:0032943	单核细胞增殖	4.41E-05	5
	GO:0042110	T细胞活化	4.44E-05	6
	GO:0045580	T细胞分化的调节	4.64E-05	4
GO-MF	GO:0031735	CCR10趋化因子受体结合	6.24E-06	2
	GO:0048248	CXCR3趋化因子受体结合	2.08E-05	2
	GO:0008009	趋化因子的活动	4.99E-05	3
	GO:0042379	趋化因子受体结合	0.000158	3
	GO:0045236	CXCR趋化因子受体结合	0.000314	2
	GO:0019865	免疫球蛋白结合	0.000517	2
	GO:0023026	MHC II类蛋白复合物结合	0.000714	2
	GO:0023023	MHC蛋白复合物结合	0.001271	2
	GO:0031724	CXCR5趋化因子受体结合	0.00147	1
	GO:0048020	CCR趋化因子受体结合	0.002251	2
KEGG	hsa04640	造血细胞谱系	4.34E-05	4
	hsa04062	趋化因子信号通路	0.000561	4
	hsa04662	B细胞受体信号通路	0.000605	3
	hsa04061	病毒蛋白与细胞因子和细胞因子受体的相互作用	0.001079	3

分类	ID	功能	P值	基因数目
GO-BP	GO:0030098	淋巴细胞分化	1.00E-05	6
	GO:0042100	B细胞增殖	1.01E-05	4
	GO:0045621	淋巴细胞分化的正向调节	1.22E-05	4
	GO:1903131	单核细胞分化	2.10E-05	6
	GO:1990266	中性粒细胞迁移	2.30E-05	4
	GO:0022409	细胞-细胞黏附的正向调节	3.93E-05	5
	GO:0046651	淋巴细胞增殖	4.20E-05	5
	GO:0032943	单核细胞增殖	4.41E-05	5
	GO:0042110	T细胞活化	4.44E-05	6
	GO:0045580	T细胞分化的调节	4.64E-05	4
GO-MF	GO:0031735	CCR10趋化因子受体结合	6.24E-06	2
	GO:0048248	CXCR3趋化因子受体结合	2.08E-05	2
	GO:0008009	趋化因子的活动	4.99E-05	3
	GO:0042379	趋化因子受体结合	0.000158	3
	GO:0045236	CXCR趋化因子受体结合	0.000314	2
	GO:0019865	免疫球蛋白结合	0.000517	2
	GO:0023026	MHC II类蛋白复合物结合	0.000714	2
	GO:0023023	MHC蛋白复合物结合	0.001271	2
	GO:0031724	CXCR5趋化因子受体结合	0.00147	1
	GO:0048020	CCR趋化因子受体结合	0.002251	2
KEGG	hsa04640	造血细胞谱系	4.34E-05	4
	hsa04062	趋化因子信号通路	0.000561	4
	hsa04662	B细胞受体信号通路	0.000605	3
	hsa04061	病毒蛋白与细胞因子和细胞因子受体的相互作用	0.001079	3