Analysis of hub genes and immune cells in the co-pathogenesis of Sjögren's syndrome and thyroid cancer based on bioinformatics

OBJECTIVE Analyzed the hub genes and immune cells involved in the co-pathogenesis of Sjögren's syndrome and thyroid cancer by bioinformatics methods.METHODS The data of Sjögren's syndrome and hyroid cancer were downloaded from GEO database, differentially expressed genes (DEGs) of Sjögren's syndrome and hyroid cancer were analyzed by R software, enrichment analysis of common DEGs was performed, common hub genes of Sjögren's syndrome and hyroid cancer were identified by using STRING database and Cytoscape software, and hub genes were verified by external datasets. Immune infiltration analysis was further performed to screen the common key immune cells of Sjögren's syndrome and hyroid cancer, and to analyze the relationship between the key immune cells and the hub genes. The NetworkAnalyst database was used to screen miRNAs and regulatory factors associated with the hub genes, and the Drug Signature Database (DSigDB) was used to screen drugs and drug targets associated with the hub genes.RESULTS The Sjögren's syndrome dataset screened 979 up-regulated genes and 761 down-regulated genes, and the hyroid cancer dataset screened 481 up-regulated genes and 423 down-regulated genes, and 93 co-expression DEGs were obtained after taking the intersection, including 73 up-regulated genes and 20 down-regulated genes. The hub gene CXCL10 was screened using three algorithms in Cytoscape's CytosHubba plug-in and verified by the dataset, and its area under the curve (AUC) in both Sjögren's syndrome and hyroid cancer was >0.7. Immune cell infiltration analysis showed that neutrophils were significantly up-regulated in both Sjögren's syndrome and hyroid cancer, and were significantly positively correlated with CXCL10. Thirty-one target miRNAs and six regulators associated with the hub gene CXCL10 were screened from the NetworkAnalyst database, and the top 10 potential therapeutic agents and targets for CXCL10-related diseases were screened from DSigDB.CONCLUSION CXCL10 is the hub gene in the co-pathogenesis of Sjögren's syndrome and hyroid cancer, and neutrophils have increased immune infiltration in Sjögren's syndrome and hyroid cancer and positively correlate with the CXCL10 gene as key immune cells.

**研究目的** 本研究通过生物信息学方法，解析参与干燥综合征（Sjögren's syndrome）与甲状腺癌协同致病过程的核心基因及免疫细胞。
**研究方法** 本研究从GEO数据库（Gene Expression Omnibus）下载干燥综合征与甲状腺癌的相关数据集，借助R软件分析两种疾病的差异表达基因（differentially expressed genes, DEGs），对二者的共有DEGs开展富集分析；通过STRING数据库与Cytoscape软件筛选干燥综合征与甲状腺癌的共有核心基因，并利用外部数据集对核心基因进行验证。进一步开展免疫浸润分析，筛选两种疾病共有的关键免疫细胞，并解析关键免疫细胞与核心基因之间的关联。使用NetworkAnalyst数据库筛选与核心基因相关的微小RNA（miRNAs）及调控因子，同时借助药物特征数据库（Drug Signature Database, DSigDB）筛选与核心基因相关的药物及药物靶点。
**研究结果** 干燥综合征数据集筛选得到979个上调基因与761个下调基因，甲状腺癌数据集筛选得到481个上调基因与423个下调基因；取二者交集后共获得93个共有差异表达基因，其中上调基因73个、下调基因20个。通过Cytoscape软件的CytosHubba插件内置的三种算法筛选得到核心基因CXCL10，并经数据集验证，该基因在干燥综合征与甲状腺癌样本中的曲线下面积（area under the curve, AUC）均大于0.7。免疫细胞浸润分析显示，中性粒细胞在干燥综合征与甲状腺癌中均显著上调，且与CXCL10基因呈显著正相关。从NetworkAnalyst数据库中筛选得到31个与CXCL10相关的靶微小RNA及6个调控因子，从DSigDB中筛选得到CXCL10相关疾病的前10种潜在治疗剂与靶点。
**研究结论** CXCL10是干燥综合征与甲状腺癌协同致病过程中的核心基因；中性粒细胞在两种疾病中均存在免疫浸润增加的现象，且与CXCL10基因呈正相关，为两种疾病的关键免疫细胞。