https://orcid.org/0000-0003-1412-6045
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Abstract
Background
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.
Data Sharing Statement
The original contributions presented in the study are publicly available. This data can be found here: Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) (Accessions: GSE84844, GSE173808, and GSE159574).
Ethics Approval and Informed Consent
The use of specimens was carried out with the participants’ written informed consent in accordance with the principles of the Declaration of Helsinki. Our research was approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang Chinese Medical University (2021-LW-015-01). All participant records/information was anonymized and de-identified before analysis. Because this was an observational study and not a clinical trial, it was not registered in a clinical trials registry.
Acknowledgments
Donghai Zhou and Xue Yu are co-first authors for this study. Xinchang Wang and Qiao Wang are co-correspondence authors for this study. We thank the contributors of the GEO (http://www.ncbi.nlm.nih.gov/geo/) database for sharing their data on open access.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. Xinchang Wang and Qiao Wang are conjointly designated as corresponding authors.
Disclosure
The authors declared that there are no conflicts of interest in this work.