Identification of key genes in salivary gland in Sjögren’s syndrome complicated with Hashimoto thyroiditis: Common pathogenesis and potential diagnostic markers

Abstract

The coexistence of Sjögren’s syndrome (SS) and Hashimoto thyroiditis (HT) has been confirmed, but the common mechanism of its co-occurrence remains unknown. This study aims to further explore the underlying mechanism and biomarkers for the co-occurrence of SS and HT. The Gene Expression Omnibus databases were used to obtain gene expression profiles for SS (GSE127952 and GSE23117) and HT (GSE29315 and GSE138198). Following identifying SS and HT’s shared differentially expressed genes, functional annotation, protein–protein interaction network creation, and module assembly were performed to discover hub genes. H&E staining and immunohistochemistry were performed to validate the expression of the hub genes in salivary glands. Finally, the receiver operating characteristic (ROC) curve was utilized to assess the discrimination of the hub genes as biomarkers in predicting SS, this study applied CIBERSORTx to analyze the immune infiltration in SS and HT in addition. A total of 48 common differentially expressed genes (48 upregulated genes and 0 downregulated genes) were chosen for further investigation. We analyzed the expression and function of PTPRC, CD69, IKZF1, and lymphocyte cytosolic protein 2 via H&E, immunohistochemistry, and ROC analysis. The 4 hub genes were mainly enriched in the T-cell receptor signaling pathway. We then evaluated and verified the diagnosis value of 4 hub genes in clinical minor labial gland biopsy of SS with HT, SS without HT, and non-SS. ROC analysis revealed that the 4 hub genes had a strong diagnostic value. Our study showed the common pathogenesis of SS and HT. These hub genes and diagnostic models may put forward some new insights for diagnosing and treating SS complicated with HT.