Exploring shared genes and molecular mechanisms between primary Sjögren's syndrome and pulmonary hypertension based on transcriptome data

Background: Primary Sjogren's syndrome (pSS) is a chronic inflammatory autoimmune disease that mainly invades the salivary gland and lacrimal gland. Compared with other populations, pSS in Asian populations is more prone to pulmonary hypertension (PAH). Most of the studies on pSS-PAH are case-control studies with a small sample size, and few studies have explored its pathogenesis, especially at the gene level. The goal of this work is to investigate the shared molecular mechanism of the pSS and PAH genes. Methods: After obtaining the expression profiles of pSS and PAH from the GEO database, we used limma software package to find the differential expression genes (DEGs) between the two diseases. In addition, we built protein-protein interaction (PPI) networks, carried out GeneMANIA analysis, immune infiltration analysis, gene set enrichment analysis (GSEA), TF-miRNA-hub regulatory network analysis, and chemical-gene interaction network analysis on these DEGs. Furthermore, the accuracy of the hub genes was evaluated using receiver operating characteristic (ROC) curves. Results: As shared DEGs between pSS and PAH, we found a total of 18 elevated genes. The findings of the enrichment analysis revealed that these genes primarily regulate the viral immune defense response and the type I interferon signaling pathway. In the ROC curve study, six hub genes (IFIT2, IFIT3, RSAD2, PARP9, GBP1, and EPSTI1) shown good sensitivity and specificity. Immune infiltration study revealed that in both the pSS and PAH cohorts, Monocyte, MDSC, Central memory CD8 T cell, and Activated CD8 T cell had a high infiltration level. A TF-miRNA-hub regulatory network was built using validation data from databases, and it included 7 transcription factors (TFs), 157 miRNAs, and 6 hub genes. The CTD database constructed a Chemical–Gene network that included 204 chemicals and 6 hub genes, among which 4 chemicals were targeted by these 6 hub genes. Conclusion: The six hub genes (IFIT2, IFIT3, RSAD2, PARP9, GBP1, and EPSTI1) might be exploited as biomarkers and therapeutic targets for pSS and PAH therapy. And they may play a biological function through modulating the viral immune defense response and the type I interferon signaling pathway. Cyclosporin may be an effective treatment for pSS in combination with PAH.