基于GEO数据库筛选垂体泌乳素瘤发生的关键差异基因

Bioinformatics analysis of key differential genes involved in the progression of prolactinoma based on GEO database

目的利用GEO数据库探究泌乳素瘤发生发展过程中的差异基因及潜在的相互作用机制,为泌乳素瘤的研究和治疗提供新的靶点。方法挑选GEO数据库GSE119063为研究对象,使用R语言筛选出芯片中的差异基因,利用筛选出的基因进行功能富集分析,构建蛋白质互相作用网络图,探究泌乳素瘤发生发展的相关机制。结果筛选出泌乳素瘤与正常垂体组织之间的差异基因279个,其中表达上调基因23个,表达下调基因256个。基因本体(gene ontology,GO)富集分析显示,差异基因主要分布于细胞外基质、内质网内腔等细胞结构,主要参与生殖、感官及视觉系统的发育、受体配体活动、生长因子活性、跨膜受体蛋白酪氨酸激酶活性等分子功能。通过对京都基因与基因百科全书(kyoto encyclopedia of genes and genonmes,KEGG)通路富集分析发现,差异基因主要在TGF-β信号通路、干细胞多能性调控信号通路、视黄醇新陈代谢通路等通路上富集。通过蛋白质互相作用网络,进一步挖掘得到可能参与垂体瘤发生发展的20个关键基因,包括SOX2、PAX6、SOX9、POMC等。结论本研究筛选得到SOX2、PAX6、SOX9、POMC等垂体泌乳素瘤发生的关键差异基因,并发现其主要通过影响TGF-β信号通路,从而影响泌乳素瘤的发生发展,可为后续泌乳素瘤的基础研究和治疗提供新靶点。

Objective To explore the differential genes involved in the progression of prolactinoma and their potential interactions based on Gene Expression Omnibus(GEO)database,thereby providing new targets for the investigation and treatment of prolactinoma.Methods The microarray GSE119063 was selected for our study,and the differentially expressed genes werescreened by R language.Gene ontology(GO)enrichment analysis,kyoto encyclopedia of genes and genonmes(KEGG)pathway analysis and protein-protein interaction(PPI)were performed to further investigate the mechanism for the initiation and progression of prolactinoma.Results Comparison between prolactinoma tumor tissues and normal tissues revealed that 279 mRNAs(23 up-regulated and 256 down-regulated)were differentially expressed.GO analysis showed that these genes were mainly located at extracellular matrix and endoplasmic reticulum lumen.For biological processes and molecular function,they were significantly enriched in eye and reproductive system development,receptor ligand activity,growth factor activity,transmembrane receptor protein tyrosine kinase activity,etc.The KEGG pathway analysis revealed that these genes were mainly involved in TGF-βsignaling pathway,signaling pathways regulating pluripotency of stem cells and retinol metabolism.Through construction of PPI,20 genes which may play key roles inprolactinoma were further identified,including SOX2,PAX6,SOX9 and POMC.Conclusion Our study found a series of differentially expressed genes(SOX2,PAX6,SOX9,POMC,etc.)which mainly impacts the progression of prolactinoma via TGF-βsignaling pathway.Our findings might provide new targets for the fundamental research and treatment of prolactinoma.