基于生物信息学分析干燥综合征和甲状腺癌共同发病的核心基因与免疫细胞  

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

作　　者：王有福 苏奕明 罗长志[1] 覃祥龙 陈子康 龚玲 侯培勇[1] WANG Youfu;SU Yiming;LUO Changzhi;QIN Xianglong;CHEN Zikang;GONG Ling;HOU Peiyong(Department of General Surgery,the Fourth Affiliated Hospital of Guangxi Medical University,Guangxi Zhuang Autonomous Region,Liuzhou545005,China;Fourth Clinical Medical College,Guangxi Medical University,Guangxi Zhuang Autonomous Region,Liuzhou545005,China)

机构地区：[1]广西医科大学第四附属医院普通外科,广西柳州545005 [2]广西医科大学第四临床医学院,广西柳州545005

出　　处：《中国医药导报》2024年第35期29-38,共10页China Medical Herald

摘　　要：目的 应用生物信息学的方法分析干燥综合征(SS)合并甲状腺癌(TC)的共同发病基因及免疫细胞,为疾病的发病机制研究提供新思路。方法 从GEO数据库下载SS(GSE40611、GSE84844)和TC(GSE33630、GSE65144)基因表达数据集,用R语言(4.3.1版本)分析两者的差异表达基因(DEGs),对共同DEGs进行富集分析,使用STRING数据库和Cytoscape软件鉴定出两者共同发病的核心基因,并利用基因表达数据集对核心基因进行验证。进一步进行免疫浸润分析,筛选SS和TC的共同关键免疫细胞,并分析关键免疫细胞与核心基因的关系。通过Network Analyst数据库筛选出与核心基因相关miRNA和调控因子,Drug Signature数据库(DSig DB)筛选出与核心基因相关的药物及药物靶点。结果 SS数据集筛选出了979个上调基因和761个下调基因,TC数据集筛选出了481个上调基因和423个下调基因,取交集后得到93个共同DEGs,其中73个上调基因,20个下调基因。利用Cytoscape的Cytos Hubba插件中3种算法筛选出了核心基因CXCL10,经验证,CXCL10在SS数据集GSE40611、GSE84844和TC数据集GSE33630、GSE65144中的曲线下面积(AUC)均>0.7。免疫细胞浸润分析结果显示,中性粒细胞在SS数据集GSE40611和TC数据集GSE33630中显著上调,且与CXCL10呈正相关(P<0.05),相关系数分别为0.41和0.32。从Network Analyst数据库筛选出了与核心基因CXCL10相关的31个靶点miRNA和6个调控因子,从DSig DB中筛选与CXCL10相关疾病的前10种潜在治疗药物和靶点。结论 CXCL10可能是SS和TC共同发病的核心基因,中性粒细胞浸润在SS和TC中发挥重要作用,可能是关键免疫细胞。Objective To analyze the common pathogenesis genes and immune cells in Sjogren’s syndrome(SS)combined with thyroid cancer(TC)using bioinformatics methods,and to provide new insights into the mechanisms of disease development.Methods Gene expression data for SS(GSE40611,GSE84844)and TC(GSE33630,GSE65144)were downloaded from the GEO database.Differentially expressed genes(DEGs)were analyzed using R software(version 4.3.1).Enrichment analysis was performed on the common DEGs,and hub genes involved in both conditions were identified using the STRING database and Cytoscape software.Validation of these hub genes was conducted using gene expression datasets.Further immune infiltration analysis was performed to identify key immune cells common to SS and TC,along with an analysis of the relationship between key immune cells and hub genes.The NetworkAnalyst database was used to identify miRNA and regulatory factors associated with hub genes,and the Drug Signature database(DSigDB)was utilized to find related drugs and drug targets.Results The SS dataset identified 979 upregulated genes and 761 downregulated genes,while the TC dataset revealed 481 upregulated genes and 423 downregulated genes.The intersection yielded 93 common DEGs,including 73 upregulated and 20 downregulated genes.The CytosHubba plugin in Cytoscape applied three algorithms to filter the hub gene CXCL10,after validation,the area under the curve(AUC)for CXCL10 in the SS datasets GSE40611 and GSE84844,as well as in the TC datasets GSE33630 and GSE65144 was all>0.7.Immune cell infiltration analysis indicated that neutrophils were significantly up-regulated in SS dataset GSE40611 and TC dataset GSE33630 and were significantly positively correlated with CXCL10(P<0.05)with correlation coefficients of 0.41 and 0.32,respectively.NetworkAnalyst identified 31 target miRNA and six regulatory factors associated with CXCL10,while DSigDB provided the top ten potential therapeutic drugs and targets related to CXCL10.Conclusion CXCL10 serves as a hub gene in the pathogen

关 键 词：干燥综合征 甲状腺癌 生物信息学 CXCL10 中性粒细胞 

分 类 号：R318.04[医药卫生—生物医学工程]