烟草暴露对孕妇胎盘组织基因表达谱的影响

Effects of tobacco exposure on gene expression profile in maternal placental tissue

摘要:

目的： 通过生物信息学分析烟草暴露与非暴露孕妇的差异表达基因谱（differentially expressed genes，DEGs），对DEGs涉及的功能进行分析预测，并找出关键基因。方法： 从公共基因芯片数据平台（gene expression omnibus，GEO）检索吸烟对孕妇基因表达谱作用研究的mRNA基因芯片数据集GSE30032，通过GEO2R分析得到DEGs，并进一步用DAVID数据库对靶基因进行基因本体论（gene ontology，GO）和KEGG信号通路富集分析，应用Cytoscape软件对模块中基因的共表达关系可视化，筛选关键基因；应用GeneMANIA数据库进一步对蛋白相互作用进行分析。结果： 共筛选出34个烟草暴露与非暴露孕妇的差异表达基因，其中24个mRNA表达上调，10个mRNA表达下调（筛选标准：FC≥1.5，P<0.05）。GO分析显示DEGs生物学过程主要涉及转录正向调控（P=0.009）、细胞对铁离子的反应（P=0.013）等；KEGG分析显示DEGs主要和肿瘤相关通路（P=0.016）和乙型肝炎（P=0.038）等信号通路有关。蛋白质相互作用网络筛选出CDKN1A、SFN和TFAP2A等8个关键基因；GeneMANIA数据库显示蛋白之间相互作用中蛋白共表达和物理相关性共占91.62%，是其相互作用的主要方式。结论： 本课题通过多平台数据库有效筛选和分析孕妇烟草暴露后的相关差异表达基因，为进一步探讨烟草作用的靶点及分子机制提供思路。

Abstract:

Objective: To explore significant differentially expressed genes (DEGs) through bioinformatics in tobacco exposed pregnant women and find Hub genes by analyzing and predicting the involved function of DEGs. Methods: The human mRNA gene chip dataset GSE30032 was extracted from common gene chip data platform of gene expression omnibus (GEO). GEO2R analysis was performed to obtain DEGs, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) signal pathway enrichment analysis were performed on the basis of DAVID database, the cytoscape software was used to construct the pathway network and GeneMANIA database was utilized for further protein interaction analysis. Results: A total of 34 DEGs were screened, of which 24 mRNAs were up-regulated and 10 mRNAs were down-regulated (FC≥1.5&P<0.05). GO analysis indicated that several functional pathways, such as positive regulation of transcription (P=0.009) and cellular response to iron ion (P=0.013) were enriched, and KEGG analysis showed the DEGs were enriched in prostate cancer (P=0.016) and hepatitis B (P=0.038) KEGG pathways. Eight genes including CDKN1A, SFN, TFAP2A and others were identified as Hub genes. GeneMANIA database showed that protein co-expression and physical interactions were the primary interaction pattern, accounting for 91.62%. Conclusion: This paper effectively screens and analyzes DEGs after pregnant women exposing to tobacco via various databases, providing thoughts for further investigating tobacco-functioned targets and molecular mechanism.