目的：通过生物信息学方法分析与重度抑郁症分子生物学机制相关的关键基因和信号通路。方法：从美国国家生物技术信息中心网站GEO公共数据库获得脑皮质总mRNA表达谱数据（GSE101521），使用Networkanalyst在线数据库筛选正常组（非精神病人）和抑郁组（抑郁症患者）存在表达差异的基因；利用DAVID和KOBAS在线数据库进行GO功能和KEGG信号通路分析；STRING和Cytoscape软件进行PPI分子网络构建。结果：共筛选出41个差异基因，其中39个差异基因上调，2个差异基因下调。GO功能注释富集分析发现差异基因主要参与炎症反应，而KEGG通路分析表明与抑郁相关的最主要通路是IL-17信号通路，TNF信号通路和NOD样受体信号通路。通过蛋白-蛋白互作网络和模块分析筛选出了6个关键基因（IL6，CXCL8，IL1B，FOS，CCL2和CXCL2）。结论：本研究筛选出了重度抑郁症涉及免疫系统新的标志物和靶标，其参与了重度抑郁症关键发病机制。

Objective： To identify key genes and pathways associated with the molecular biological mechanisms of major depressive disorder through bioinformatics analysis in the Gene Expression Omnibus （GEO） public database of the National Center for Biotechnology Information website. Methods：The whole-transcriptome brain expression profile dataset （GSE101521） was obtained from the GEO database. Differentially-expressed genes （DEGs） in the normal group （non-psychiatric human） and the MDD group （depressive patients） were identified by applying Networkanalyst online database. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were performed to function annotation and enrichment analysis. After that， STRING online database was conducted to protein–protein interaction （PPI） network， and Cytoscape.3.7.2 software was performed to module analysis. Results： Out of the 41 DEGs identified from normal tissue samples and MDD， 39 were upregulated and 2 were downregulated. GO enrichment analysis discovered that DEGs were primarily involved in inflammatory response， and KEGG pathway analysis suggested that the most chiefly pathways related to MDD were IL-17 signaling pathway， TNF signaling pathway and NOD-like receptor signaling pathway. Six hub genes （IL6， CXCL8， IL1B， FOS， CCL2， and CXCL2） were identified by PPI network and module analysis. Conclusion： Our current study detected novel markers and targets involved immune system， which are involved in pivotal biological mechanisms related to the pathogenesis of major depression. Looking forward， these findings still need to be validated in future experimental studies.

R749.4；Q811.4

国家自然科学基金资助项目（81973502）