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

OBJECTIVE: Reveal key genes involved in the pathogenesis of Primary Sjogren'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.