Integrated Analysis Identifies Upregulated SAMD9L as a Potential Biomarker Correlating with the Severity of Primary Sjögren’s Syndrome

Abstract

Donghai Zhou,1,* Xue Yu,2,* Kai Yu,3 Yating Ren,2 Kepeng Yang,1 Xinchang Wang,1 Qiao Wang4 1Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China; 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China; 3Department of Hepatology 1, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang Province, 310023, People’s Republic of China; 4College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiao Wang; Xinchang Wang, Email [email protected]; [email protected]: Primary Sjögren’s syndrome (pSS) is an autoimmune disease with lymphocytic infiltration of the salivary and lachrymal glands, whose present disease-specific objective indicators are few and have shortcomings that should be addressed. An integrated analysis of sequencing data from different cohorts has the potential to unveil novel biomarkers in pSS.Methods: We identified 3 GEO datasets, including gene expression data from minor salivary gland (MSG) biopsy samples of 49 patients with pSS and 31 non-pSS and whole blood cells of 30 pSS patients and 30 healthy controls (HCs). Differentially expressed genes (DEGs) involved in pSS were identified from these datasets. Function Enrichment Analyses of common upregulated DEGs and PPI (protein-protein interaction) networks were performed. Furthermore, we have carried out further analysis of these DEGs to explore their potential clinical significance and diagnostic efficacy as a biomarker for pSS. Sterile Alpha Motif Domain Containing 9 Like (SAMD9L), one of the DEGs, has been identified as a promising candidate biomarker that correlates with the severity of pSS. This has been validated by analyzing local clinical samples from 30 pSS and non-pSS patients’ MSG biopsies, as well as serum samples of 18 pSS and HC individuals. Finally, we performed correlation analysis to understand the relationship between SAMD9L and infiltrated immune cells.Results: We identified 10 common highly expressed DEGs in pSS of different tissues. These genes were mainly involved in virus infection-related pathways and inferno-related pathways. GEO data and our clinical data showed that SAMD9L increases with disease severity. Public and local cohorts showed that SAMD9L has high diagnostic performance (AUC=0.845– 0.867) as a biomarker, and its AUC was comparable to the Focus score when combined with RF or SSA.Conclusion: Up-regulated SAMD9L may serve as a promising novel pSS diagnostic biomarker and have potential value for evaluating the severity of pSS.Keywords: Sjögren’s syndrome, SAMD9L, biomarker, integrated analysis

Keywords

• sjögren's syndrome
• samd9l
• biomarker
• integrated analysis