综合分析确定上调的SAMD9L作为与原发性干燥综合征严重程度相关的潜在生物标志物。
Integrated Analysis Identifies Upregulated SAMD9L as a Potential Biomarker Correlating with the Severity of Primary Sjögren's Syndrome.
作者信息
Zhou Donghai, Yu Xue, Yu Kai, Ren Yating, Yang Kepeng, Wang Xinchang, Wang Qiao
机构信息
Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People's Republic of China.
The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People's Republic of China.
出版信息
J Inflamm Res. 2023 Aug 28;16:3725-3738. doi: 10.2147/JIR.S413581. eCollection 2023.
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.
背景
原发性干燥综合征（pSS）是一种自身免疫性疾病，其特征为唾液腺和泪腺出现淋巴细胞浸润，目前针对该疾病的特异性客观指标较少且存在有待解决的缺点。对不同队列的测序数据进行综合分析有可能揭示pSS中的新型生物标志物。
方法
我们识别了3个基因表达综合数据库（GEO）数据集，包括49例pSS患者和31例非pSS患者的小唾液腺（MSG）活检样本的基因表达数据，以及30例pSS患者和30例健康对照（HC）的全血细胞数据。从这些数据集中识别出参与pSS的差异表达基因（DEG）。对共同上调的DEG进行功能富集分析并构建蛋白质-蛋白质相互作用（PPI）网络。此外，我们对这些DEG进行了进一步分析，以探索它们作为pSS生物标志物的潜在临床意义和诊断效能。含无菌α基序结构域9样蛋白（SAMD9L）作为DEG之一，已被确定为与pSS严重程度相关的有前景的候选生物标志物。通过分析30例pSS和非pSS患者的MSG活检局部临床样本以及18例pSS患者和HC个体的血清样本对其进行了验证。最后，我们进行了相关性分析以了解SAMD9L与浸润免疫细胞之间的关系。
结果
我们在不同组织的pSS中识别出10个共同高表达的DEG。这些基因主要参与病毒感染相关途径和炎症相关途径。GEO数据和我们的临床数据表明，SAMD9L随疾病严重程度增加。公共队列和局部队列表明，SAMD9L作为生物标志物具有较高的诊断性能（曲线下面积[AUC]=0.845-0.867），当与类风湿因子（RF）或抗干燥综合征A抗原（SSA）联合使用时，其AUC与聚焦评分相当。
结论
上调的SAMD9L可能是一种有前景的新型pSS诊断生物标志物，对评估pSS的严重程度具有潜在价值。
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