Evaluation of key genes and biological pathways that play a role in primary Sjogren syndrome by using a systems biology approach
Iranian Journal of Pharmaceutical Sciences,
دوره 19 شماره 1 (2023),
15 January 2023
,
صفحه 50-60
https://doi.org/10.22037/ijps.v19i1.41962
چکیده
Primary Sjogren syndrome (PSS) is one of the most common systemic autoimmune diseases. Lymphocytic infiltration of exocrine glands, especially lacrimal and salivary in PSS, causes ocular and oral dryness. Dry mouth may lead to difficulty in speaking, chewing, and swallowing and result in reduced quality. The pathogenesis of PSS involves multiple factors, such as genetic, environmental, and immunological factors. Despite extensive research over the last few decades, the exact etiology and progression of PSS and its inflammatory lesions is still unknown. Gene co-expression network analysis (WGCNA) is a system biology method that can be used to describe the correlation between different genes and find modules of highly correlated genes and key genes. Also, by using these modules, we can get gene ontology information and biological pathways. In this study, we used WGCNA to analyze the GSE40611 dataset, which consists of 17 PSS patients and 18 healthy controls. We construct a co-expression network for mRNA expression data of patients and control groups and then find the most significant module and hub genes that play important roles in PSS. We also identify biological pathways and related miRNA for hub genes. Among all the modules, turquoise had the most correlation with PSS and some of the hub genes, including GPR18, FCRL1, VNN2 and etc. Also, a large number of pathways were identified in the turquoise module, most of them related to immune system activity, like T-cell activation, lymphocyte differentiation, leukocyte and lymphocyte activation, regulation of immune system processes, regulation of immune response, and cell-cell adhesion. External validation using bulk RNA sequencing data also confirmed the presence of selected hub-genes in pathogenicity of PSS. Finally, these results can lead to finding key players in treatment of PSS.
- Primary Sjogren syndrome
- Systems biology
- WGCNA
- Microarray
- Bulk RNA sequencing
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مراجع
Holdgate, N. and E.W.S. Clair, Recent advances in primary Sjogren's syndrome, F1000Research (2016) 5.
Chen, X., et al., Elevated cytokine levels in tears and saliva of patients with primary Sjögren’s syndrome correlate with clinical ocular and oral manifestations, Sci Rep (2019) 9(1): 1-10.
Rizzo, C., et al., Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation, Vaccines (Basel) (2020) 8(2): 272.
Retamozo, S., P. Brito-Zerón, and M. Ramos-Casals, Prognostic markers of lymphoma development in primary Sjögren syndrome, Lupus (2019) 28(8): 923-936.
Bolstad, A.I. and K. Skarstein, Epidemiology of Sjögren’s Syndrome—from an Oral Perspective, Curr Oral Health Rep (2016) 3(4): 328-336.
Molano-González, N., et al., Anti-citrullinated protein antibodies and arthritis in Sjögren’s syndrome: a systematic review and meta-analysis, Scand J Rheumatol (2019) 48(2): 157-163.
Wang, J., L. Zhou, and B. Liu, Update on disease pathogenesis, diagnosis, and management of primary Sjögren’s syndrome, Int J Rheum Dis (2020).
Nocturne, G. and X. Mariette, B cells in the pathogenesis of primary Sjögren syndrome, Nat Rev Rheumatol (2018) 14(3): 133.
Martín-Nares, E. and G. Hernández-Molina, Novel autoantibodies in Sjögren's syndrome: a comprehensive review, Autoimmun Rev (2019) 18(2): 192-198.
Verstappen, G.M., F.G. Kroese, and H. Bootsma, T cells in primary Sjögren’s syndrome: targets for early intervention, Rheumatology (2019).
Groups, S.s.I.C.C.A.R., Natural History and Predictors of Progression to Sjögren's Syndrome Among Participants of the Sjögren's International Collaborative Clinical Alliance Registry, Arthritis Care Res (2018) 70(2): 284-294.
Xin, M., et al., Mirt2 functions in synergy with miR-377 to participate in inflammatory pathophysiology of Sjögren's syndrome, Artif Cells Nanomed Biotechnol (2019) 47(1): 2473-2480.
Sarkar, P.K., et al., Pulmonary manifestations of primary Sjogren's syndrome, Indian J Chest Dis Allied Sci (2009) 51(2): 93-101.
Alberghina, L. and H.V. Westerhoff, Systems biology: definitions and perspectives, Vol. 13. 2007: Springer Science & Business Media.
Tandon, M., The Immune-Epithelial Interaction in the Pathogenesis of Primary Sjögren's Syndrome, Thomas Jefferson University (2017)
Zou, Y. and M.D. Laubichler, From systems to biology: A computational analysis of the research articles on systems biology from 1992 to 2013, PLoS One (2018) 13(7): e0200929.
Tavassoly, I., J. Goldfarb, and R. Iyengar, Systems biology primer: the basic methods and approaches, Essays Biochem (2018) 62(4): 487-500.
Klassen, A., et al., Metabolomics: Definitions and significance in systems biology, in Metabolomics: From Fundamentals to Clinical Applications, Springer (2017): 3-17.
Langfelder, P. and S. Horvath, WGCNA: an R package for weighted correlation network analysis, BMC Bioinformatics (2008) 9(1): 559.
Hu, S., et al., Systems biology analysis of sjögren's syndrome and mucosa‐associated lymphoid tissue lymphoma in parotid glands, Arthritis & Rheumatism (2009) 60(1): 81-92.
Presson, A.P., et al., Integrated weighted gene co-expression network analysis with an application to chronic fatigue syndrome, BMC Syst Biol (2008) 2(1): 95.
Hillen, M.R., et al., Plasmacytoid DCs From Patients With Sjögren's Syndrome Are Transcriptionally Primed for Enhanced Pro-inflammatory Cytokine Production, Front immunol (2019) 10: 2096.
Yao, Q., et al., Identifying Key Genes and Functionally Enriched Pathways in Sjögren's Syndrome by Weighted Gene Co-Expression Network Analysis, Front Genet (2019) 10: 1142.
Livak, K.J. and T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method, methods (2001) 25(4): 402-408.
Kanehisa, M., et al., New approach for understanding genome variations in KEGG, Nucleic Acids Res (2019) 47(D1): D590-D595.
Bindea, G., et al., ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks, Bioinformatics (2009) 25(8): 1091-1093.
Seror, R., G. Nocturne, and X. Mariette, Current and future therapies for primary Sjögren syndrome, Nat Rev Rheumatol (2021): 1-12.
Vitali, C., et al., Management of Sjögren's syndrome: present issues and future perspectives, Front Med (2021) 8.
Travaglino, A., et al., Sjögren syndrome in primary salivary gland lymphoma: a systematic review and meta-analysis, Am J Clin Pathol (2020) 153(6): 719-724.
Wu, Z., et al., Using WGCNA (weighted gene co-expression network analysis) to identify the hub genes of skin hair follicle development in fetus stage of Inner Mongolia cashmere goat, PloS one (2020) 15(12): e0243507.
Yin, X., et al., Identification of key modules and genes associated with breast cancer prognosis using WGCNA and ceRNA network analysis, Aging (Albany NY) (2021) 13(2): 2519.
He, Y., et al., Tumor infiltrating lymphocytes associated competitive endogenous RNA networks as predictors of outcome in hepatic carcinoma based on WGCNA analysis, PloS one (2021) 16(7): e0254829.
Nourbakhsh, F., R. Atabaki, and A. Roohbakhsh, The role of orphan G protein-coupled receptors in the modulation of pain: A review, Life Sci (2018) 212: 59-69.
Morales, P., et al., Therapeutic Exploitation of GPR18: Beyond the Cannabinoids? Miniperspective, J Med Chem (2020) 63(23): 14216-14227.
Zhang, L., et al., GPR18 expression on PMNs as biomarker for outcome in patient with sepsis, Life sciences (2019) 217: 49-56.
Guerrero-Alba, R., et al., Some prospective alternatives for treating pain: the endocannabinoid system and its putative receptors GPR18 and GPR55, Front pharmacol (2019) 9: 1496.
Neumann, A., et al., Computational investigations on the binding mode of ligands for the cannabinoid-activated G protein-coupled receptor GPR18, Biomolecules (2020) 10(5): 686.
Reyes-Resina, I., et al., Molecular and functional interaction between GPR18 and cannabinoid CB2 G-protein-coupled receptors. Relevance in neurodegenerative diseases, Biochem Pharmacol (2018) 157: 169-179.
Liu, Y., et al., Omics-wide quantitative B-cell infiltration analyses identify GPR18 for human cancer prognosis with superiority over CD20, Commun Biol (2020) 3(1): 1-11.
Liu, H.-W., et al., The rs6427384 and rs6692977 Single Nucleotide Polymorphisms of the Fc Receptor-Like 5 (FCRL5) Gene and the Risk of Ankylosing Spondylitis: A Case Control Study in a Single Center in China. Med Sci Monit (2020) 26: e920956-1.
Rostamzadeh, D., et al., Update on Fc receptor-like (FCRL) family: new immunoregulatory players in health and diseases, Expert Opin Ther Targets (2018) 22(6): 487-502.
Yousefi, Z. and N. Eskandari, Prognostic significance of Fc receptor-like 1 in patients with chronic lymphocytic leukemia, hairy cell leukemia, and various B-cell non-Hodgkin's lymphoma, Leuk Res (2019) 12: 100181.
Yousefi, Z., et al., Fc Receptor-Like 1 as a Promising Target for Immunotherapeutic Interventions of B-Cell-Related Disorders, Biomarker insights (2019) 14: 1177271919882351.
Liu, Y., et al., Development and Validation of the B Cell-Associated Fc Receptor-like Molecule-Based Prognostic Signature in Skin Cutaneous Melanoma, Biomed Res Int (2020) 2020: 8509805.
Chen, Y., et al., MicroRNA‑106a regulates the proliferation and invasion of human osteosarcoma cells by targeting VNN2, Oncol Rep (2018) 40(4): 2251-2259.
Nitto, T. and K. Onodera, The linkage between coenzyme a metabolism and inflammation: roles of pantetheinase, J Pharmacol Sci (2013) 123(1): 1-8.
Guimarães, A.F.M., Vanin-2, a potential prognostic marker of resistance in acute lymphoblastic leukemia, (2015).
Bornhauser, B., et al., The hematopoietic stem cell marker VNN2 is associated with chemoresistance in pediatric B-cell precursor ALL, Blood advances (2020) 4(17): 4052-4064.
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- IJPS-41962- Vol. 19- Issue1- P. 50-60 (English) دانلود شده: 40 بار