Abstract
Abstract
Introduction
Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by inflammatory infiltration, and dysfunction of the salivary and lacrimal glands. This research aimed to explore the disease pathogenesis and improve the diagnosis and treatment of pSS by mining inflammation-associated biomarkers.
Methods
Five pSS-related datasets were retrieved from the Gene Expression Omnibus (GEO) database. Inflammation-associated biomarkers were determined by the least absolute shrinkage and selection operator (LASSO) and support vector machines recursive feature elimination (SVM-RFE). Single sample gene set enrichment analysis (ssGSEA) was implemented to profile the infiltration levels of immune cells. Real-time quantitative PCR (RT-qPCR) verified the expression of biomarkers in clinical samples.
Results
Four genes (LY6E, EIF2AK2, IL15, and CXCL10) were screened as inflammation-associated biomarkers in pSS, the predictive performance of which were determined among three pSS-related datasets (AUC > 0.7). Functional enrichment results suggested that the biomarkers were involved in immune and inflammation-related pathways. Immune infiltration analysis revealed that biomarkers were notably connected with type 2 T helper cells, regulatory T cells which were significantly expressed between pSS and control. TESTOSTERONE and CYCLOSPORINE were predicted to take effect by targeting CXCL10 and IL15 in pSS, respectively.
Conclusion
Four inflammation-associated biomarkers (LY6E, EIF2AK2, IL15, and CXCL10) were explored, and the underlying regulatory mechanisms and targeted drugs associated with these biomarkers were preliminarily investigated according to a series of bioinformatics methods based on the online datasets of pSS, which provided a reference for understanding the pathogenesis of pSS.
Key Points• Inflammation-associated biomarkers (LY6E, EIF2AK2, IL15, and CXCL10) were firstly identified in Sjögren’s syndrome based on LASSO and SVM-RFE analyses.• CXCL10, EIF2AK2 and LY6E were prominently positively correlated with immature B cells, while IL15 were significantly negatively correlated with memory B cells in Sjögren’s syndrome.• LY6E, EIF2AK2, IL15, and CXCL10 were significantly more highly expressed in clinical Sjögren’s syndrome samples compared to healthy control samples, which was consistent with the analysis results of the GEO database. •LY6E, EIF2AK2, IL15, and CXCL10 might be used as the biomarkers for the treatment and diagnosis of Sjögren’s syndrome.
Funder
The National Natural Science Foundation of China
Peking University Medicine Seed Fund for Interdisciplinary Research
Key Clinical Projects of Peking University Third Hospital
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences
Program for New Clinical Techniques and Therapies of Peking University School and Hospital of Stomatology
Publisher
Springer Science and Business Media LLC
Reference109 articles.
1. Ramos-Casals M, Brito-Zeron P, Siso-Almirall A, Bosch X (2012) Primary Sjogren syndrome. BMJ 344:e3821
2. Manfre V, Cafaro G, Riccucci I, Zabotti A, Perricone C, Bootsma H, De Vita S, Bartoloni E (2020) One year in review 2020: comorbidities, diagnosis and treatment of primary Sjogren’s syndrome. Clin Exp Rheumatol 38 Suppl 126(4):10–22
3. Medeiros CCG, Dos Anjos Borges LG, Cherubini K, Salum FG, Medina da Silva R, de Figueiredo MAZ (2018) Oral yeast colonization in patients with primary and secondary Sjogren’s syndrome. Oral Dis 24(7):1367–1378
4. Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, Gottenberg JE, Bootsma H, Mariette X, Vitali C et al (2010) EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis 69(6):1103–1109
5. Voulgarelis M, Ziakas PD, Papageorgiou A, Baimpa E, Tzioufas AG, Moutsopoulos HM (2012) Prognosis and outcome of non-Hodgkin lymphoma in primary Sjogren syndrome. Medicine (Baltimore) 91(1):1–9
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