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缺血性脑卒中患者恢复稳定期外周血单个核细胞中差异表达基因的生物信息学研究

Bioinformatic study on differential expression genes in PBMCs collected from ischemic stroke patients during convalescent phase

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【作者】 彭彬张雪曹帆帆王莹孙家兰江梅李龙宣

【Author】 PENG Bin;ZHANG Xue;CAO Fanfan;WANG Ying;SUN Jialan;JIANG Mei;LI Longxuan;Department of Neurology,Shanghai Gongli Hospital,the Second Military Medical University;

【机构】 上海市浦东新区公利医院&第二军医大学附属公利医院中法合作中心实验室上海市浦东新区公利医院&第二军医大学附属公利医院神经科

【摘要】 目的分析缺血性脑卒中(IS)患者恢复稳定期外周血单个核细胞(PBMCs)中的差异表达基因,为探讨脑卒中恢复稳定期的遗传病理机制提供生物信息学线索。方法选择GEO数据库中GDS4521芯片数据,该芯片以年龄、性别相匹配的20例IS恢复稳定期(脑卒中发生至少6个月以上)患者和20例未发生过脑卒中者作为研究对象,收集其PBMCs进行基因芯片检测,利用GEO2R、DAVID、g:profiler和String等工具,筛选和分析差异表达基因功能富集和相关信号通路情况。结果脑卒中恢复稳定期组与对照组相比,在PBMCs中发现37个基因表达明显变化,其中34个上升,3个下降。GO分析表明,这些差异表达基因在生物过程方面,以炎性反应、中性粒细胞趋化相关基因为最多;在分子功能方面,以趋化因子活性相关基因为最多。KEGG信号通路分析表明,位于TNF信号通路中的差异表达基因数量最多。相互作用网络图揭示,这些差异基因主要以与炎性反应相关的两个网络为主。结论 IS发生超过6个月后仍有多种功能蛋白和信号通路可能发生改变,特别是与炎性反应相关的蛋白和信号通路,提示炎性反应在IS的恢复稳定期仍可能对疾病的预后和再发起作用。

【Abstract】 Objective To screen differential expression genes(DEGs)in peripheral blood mononuclear cells(PBMCs)of patients with ischemic stroke(IS)during convalescent phase,and to analyze their functional characteristics,in order to further understand the pathologic mechanism of stroke and provide some bioinformatic clues.Methods The data of Chip GDS4521 collected from PBMCs in the convalescent phase of IS were chosen from the GEO database.GEO2 Ranalysis tools were used to search for DEGs,and the characteristics of gene function enrichment and related signal pathways in these DEGs were analyzed by DAVID,g:profiler and String.Results Compared with the normal control group,the expression of 37 genes in PBMCs was significantly changed in the IS recovery period(> 6months),34 of which were significantly increased and 3genes decreased significantly.Gene Ontology(GO)analysis showed that in biology process these DGEs were mainly involved in inflammatory process,neutrophil chemotaxis,cell proliferation and apoptosis,and signal transduction.In molecular function most of them are related to chemokine activity and receptor binding,transcription factor activity,cytokine activity,and so on.KEGG signaling pathway analysis showed that the DEGs were mainly involved in TNF,NF-κB,chemokines,TOLL-like receptors and NOD-like receptors signaling pathways.The network map of the DEGs revealed that these genes were mainly dominated by two network maps related to inflammation.Conclusions This study demonstrated that many functional proteins and multiple signaling pathways may change at least 6 months after IS,especially in inflammation-related proteins and pathways,suggesting that inflammatory response might play a key role not only in acute but also in convalescent phase of IS.

【基金】 国家自然科学基金面上项目(81571203);上海市自然科学基金项目(15ZR1437200);上海市浦东新区卫生系统领先人才培养计划(PWR12014-05);上海市医学重点专科建设计划项目(ZK2015B16);上海市卫计委科研项目(201540394);上海市卫生计生系统优秀学科带头人(百人计划)(2017BR051)
  • 【文献出处】 中国神经免疫学和神经病学杂志 ,Chinese Journal of Neuroimmunology and Neurology , 编辑部邮箱 ,2017年05期
  • 【分类号】R743.3
  • 【被引频次】1
  • 【下载频次】184
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