Transcriptomic sequencing of multiple salivary glands combined with bioinformatics analysis reveals key genes in primary Sjögren's syndrome.

IF 2.9 3区 医学 Q2 RHEUMATOLOGY
Chenchen Wang, Hongmin Hu, Yinyue Xu, Shasha Wang
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引用次数: 0

Abstract

Objective: Reveal key genes involved in the pathogenesis of Primary Sjögren's Syndrome (pSS) and identify new potential biomarkers and therapeutic targets.

Methods: mRNA transcriptome data from pSS patients'and healthy controls'parotid and minor salivary glands were collected from the Gene Expression Omnibus (GEO) database. mRNA sequencing was performed on pSS mouse model submandibular glands. Differentially expressed genes (DEGs) were identified and core genes were screened using protein-protein interaction (PPI)networks. Validation was done through Gene Ontology (GO),Kyoto Encyclopedia of Genes and Genomes (KEGG), immune cell infiltration, heatmap, and Receiver Operating Characteristic (ROC) curve analyses, followed by external validation. Finally, review the clinical studies of drugs targeting these genes.

Results: A total of 113 DEGs were identified, yielding 15core DEGs CD8 A, LCK, SYK, CD2, CD247, CD3D, LCP2, CD3G, CCR7, ITK, CXCR4, B2M, CXCL10, CXCL13, and CXCL9.These core genes were enriched in antigen receptor-mediated and T cell receptor signaling pathways, as well as in the chemokine signaling pathway. Immunocell infiltration analysis revealed that, except for B2M, the expression of other core genes is correlated with the proportion of immune cells. Genes like, CXCL13, CXCL9, CXCR4,CD2,CCR7,and ITK exhibited high diagnostic accuracy for distinguish in pSS patients. Core DEGs such as LCK, SYK, LCP2, and ITK was validated in salivary gland data from pSS patients and mouse models. Drugs targeting LCK, SYK, ITK, and other core genes, with their clinical status, were identified.

Conclusion: This study identified key genes in pSS, providing novelinsights into pathogenesis, promising biomarkers, and potential therapeutictargets. Key Points • mRNA transcriptomic sequencing was conducted on submandibular gland specimens from NOD mice simulating pSS and normal mice. • Commonly dysregulated core genes were identified across the minor and parotid salivary glands of pSS patients and healthy controls, as well as in the submandibular glands of NOD and normal mice. • ROC analysis was employed to evaluate their predictive value in the diagnosis of pSS.Genes such as CXCL13, CXCL9, CXCR4, CD2, CCR7, and ITK exhibited high diagnostic accuracy for distinguishing pSS patients. • Genes such as LCK, SYK, and ITK have been validated through external verification and qPCR, and have been identified as targets for clinical drugs.

多个唾液腺转录组测序结合生物信息学分析揭示了原发性Sjögren综合征的关键基因。
目的:揭示原发性Sjögren's综合征(pSS)发病机制的关键基因,寻找新的潜在生物标志物和治疗靶点。方法:从基因表达综合数据库(Gene Expression Omnibus, GEO)中收集pSS患者和健康对照组腮腺和小唾液腺的mRNA转录组数据。对pSS小鼠颌下腺模型进行mRNA测序。利用蛋白-蛋白相互作用(PPI)网络鉴定差异表达基因(DEGs),筛选核心基因。通过基因本体(GO)、京都基因与基因组百科全书(KEGG)、免疫细胞浸润、热图和受试者工作特征(ROC)曲线分析进行验证,然后进行外部验证。最后,综述了针对这些基因的药物的临床研究进展。结果:共鉴定出113个DEGs,产生15个核心DEGs CD8 A、LCK、SYK、CD2、CD247、CD3D、LCP2、CD3G、CCR7、ITK、CXCR4、B2M、CXCL10、CXCL13和CXCL9。这些核心基因在抗原受体介导和T细胞受体信号通路以及趋化因子信号通路中富集。免疫细胞浸润分析显示,除B2M外,其他核心基因的表达均与免疫细胞比例相关。CXCL13、CXCL9、CXCR4、CD2、CCR7和ITK等基因在pSS患者中表现出较高的诊断准确性。核心基因如LCK、SYK、LCP2和ITK在pSS患者和小鼠模型的唾液腺数据中得到验证。确定靶向LCK、SYK、ITK等核心基因的药物及其临床状况。结论:该研究确定了pSS的关键基因,为pSS的发病机制、有希望的生物标志物和潜在的治疗靶点提供了新的见解。•对模拟pSS的NOD小鼠和正常小鼠的颌下腺标本进行mRNA转录组测序。•在pSS患者和健康对照组的小涎腺和腮腺以及NOD和正常小鼠的下颌下腺中发现了常见的失调核心基因。•采用ROC分析评估其对pSS诊断的预测价值。CXCL13、CXCL9、CXCR4、CD2、CCR7、ITK等基因对pSS患者具有较高的诊断准确性。•LCK、SYK、ITK等基因已通过外部验证和qPCR验证,已被确定为临床药物的靶点。
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来源期刊
Clinical Rheumatology
Clinical Rheumatology 医学-风湿病学
CiteScore
6.90
自引率
2.90%
发文量
441
审稿时长
3 months
期刊介绍: Clinical Rheumatology is an international English-language journal devoted to publishing original clinical investigation and research in the general field of rheumatology with accent on clinical aspects at postgraduate level. The journal succeeds Acta Rheumatologica Belgica, originally founded in 1945 as the official journal of the Belgian Rheumatology Society. Clinical Rheumatology aims to cover all modern trends in clinical and experimental research as well as the management and evaluation of diagnostic and treatment procedures connected with the inflammatory, immunologic, metabolic, genetic and degenerative soft and hard connective tissue diseases.
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