Shared biomarkers of multi-tissue origin for primary Sjogren's syndrome and their importance in immune microenvironment alterations

Abstract

With the recent advancement in omics and molecular techniques, a wealth of new molecular biomarkers have become available for the diagnosis and classification of primary Sjögren's syndrome (pSS) patients. However, whether these biomarkers are universal is of great interest to us. In this study, we used various methods to obtain shared biomarkers derived from multiple tissue in pSS patients and to explore their relationship with immune microenvironment alterations. First we identified differentially expressed genes (DEGs) between pSS and healthy controls utilizing nine mRNA microarray datasets obtained from the Gene Expression Omnibus (GEO). Then, shared biomarkers were filtered out using robust rank aggregation (RRA), data integration analysis, weighted gene co-expression network analysis (WGCNA), and least absolute selection and shrinkage operator (LASSO) regression; their roles in pSS and association with changes in the immune microenvironment were also analyzed. In addition, these biomarkers were further confirmed with both the testing set and immunohistochemistry (IHC). As a result, ten biomarkers, i.e., EPSTI1, IFI44, IFIT1, IFIT2, IFIT3, MX1, OAS1, PARP9, SAMD9L and TRIM22, were identified. Receiver operating characteristic (ROC) curves showed that the ten genes could discriminate pSS from controls. Gene set enrichment analysis (GSEA) showed that the enrichment of immune-related gene sets was significant in pSS patients with high expression of either biomarker. Furthermore, the association between some immunocytes and these biomarkers was identified. In the two distinct molecular patterns of pSS patients based on the expressions of these biomarkers, the proportions of immunocytes were significantly different. Our study identified shared biomarkers of multi-tissue origin and revealed their relationship with altered immune microenvironment in pSS patients. These markers not only have diagnostic implications but also provide potential immunotherapeutic targets for the clinical treatment of pSS patients.