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首页> 中文期刊> 《中华实验眼科杂志》 >泪腺良性淋巴上皮病变与眼眶海绵状血管瘤患者病变标本中差异表达基因的检测

泪腺良性淋巴上皮病变与眼眶海绵状血管瘤患者病变标本中差异表达基因的检测

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摘要

Background Benign lymphoepithelial lesion of lacrimal gland is not a common orbital disease in clinic,which mainly presented as symmetrical and painless enlargement of bilateral lacrimal glands.However,the etiology and pathogenesis of this disease is still unclear now.Objective This study was to screen the differentially expressed genes between benign lymphoid epithelial lesion of lacrimal gland and orbital cavernous hemangioma and explore the pathogenesis of benign lymphoepithelial lesion of lacrimal gland at the molecular level.Methods Nine patients diagnosed as benign lymphoepithelial lesion of lacrimal gland in Beijing Tongren Hospital,Capital Medical University were enrolled from September 2010 to April 2013,and nine patients with orbital cavernous hemangioma served as control group.The intraorbital tissue was collected during surgery.Whole-genome gene expression microarray was used to detect the expressed genes,and limma algorithm was used to analyze the differentially expressed genes between the benign lymphoepithelial lesion of lacrimal gland and the orbital cavernous hemangioma.Real-time PCR was used to verify differentially expressed genes,Fisher method and gene ontology (GO) functional analysis were performed to realize function and signaling pathways analysis.This study complied with Helsinki Declaration and the protocol was aproved by Institutional Review Board of Beijing Tongren Hospital,and informed consent was obtained.Results Total 5 260 differentially expressed genes were screened between benign lymphoepithelial lesion of lacrimal gland and orbital cavernous hemangioma.The Fisher function and signaling pathways analysis showed that 109 GO terms were significantly upregulated and 101 GO terms were significantly downregulated,and 32 relevant signaling pathways were significantly upregulated and 25 signaling pathways were significantly downregulated in the benign lymphoepithelial lesion of lacrimal gland.GO analysis showed that the expression enrichment of complement receptormediated signaling pathway was high,then following the upregulation of T cell and B cell signaling pathways and downregulation of mitogen-activated protein kinase (MAPK) and transforming growth factor-β (TGF-β) signaling pathways.Real-time PCR results showed that the expressions of TIPRL,TLR7 and TLR10 genes were significantly higher in the benign lymphoepithelial lesion of lacrimal gland than that in the orbital cavernous hemangioma,with significant differences between the two diseases (Z =-2.03,-2.32,-2.32;all at P＜0.05),which was consistent with the microarray data.Conclusions Gene expression profiles are significantly different between benign lymphoepithelial lesion of lacrimal gland and orbital cavernous hemangioma.Those differentially expressed genes play roles in the upregulation of T cell and B cell signaling pathways,downregulation of MAPK and TGF-β signaling pathways and the change of complement system.It is implied that a comprehensive effect of various genes and pathways participates in the pathogenesis of benign lymphoepithelial lesion of lacrimal gland.%背景 泪腺良性淋巴上皮病变是临床较少见的眼眶病,主要表现为双侧泪腺的对称性、无痛性肿大,其病因和发病机制至今尚未阐明. 目的 筛选泪腺良性淋巴上皮病变组织与眼眶海绵状血管瘤患者病变组织中的差异表达基因,从分子水平探讨泪腺良性淋巴上皮病变的发病机制.方法 收集2010年9月至2013年4月在首都医科大学附属北京同仁医院经病理学检查证实的泪腺良性淋巴上皮病变患者9例的病变标本,并收集同期眼眶海绵状血管瘤患者9例的组织标本作为对照.利用全基因组表达谱芯片技术和limma算法检测2个组患者组织标本中的差异表达基因,并采用实时荧光定量PCR法验证差异基因的表达,采用Fisher法和基因本体(GO)功能富集分析法对差异表达基因进行功能分析和信号通路分析,找到主要差异表达基因的功能群和信号通路. 结果 泪腺良性淋巴上皮病变患者与眼眶海绵状血管瘤患者中共筛选出5 260个差异基因,Fisher差异表达基因的功能显著性分析和信号通路分析显示,109个GO条目中的差异表达基因显著上调,101个GO条目中的差异表达基因显著下调,其中32个功能基因相关的信号通路显著上调,25个信号通路显著下调.GO分析显示,差异表达基因中补体受体介导的信号通路表达丰度最高,其次为T细胞信号通路和B细胞信号通路上调以及丝裂原激活蛋白激酶(MAPK)信号通路和转化生长因子-β(TGF-β)信号通路下调.实时荧光定量PCR结果显示,泪腺良性淋巴上皮病变组患者标本中TIPRL、TLR7和TLR10基因的相对表达量明显高于眼眶海绵状血管病组,差异均有统计学意义(Z=-2.03、-2.32、-2.32,均P＜0.05),与基因芯片检测结果一致.结论 人泪腺良性淋巴上皮病变组织与眼眶海绵状血管瘤病变组织中基因表达谱明显不同,这些差异表达基因除参与T细胞和B细胞信号通路的上调以及MAPK信号通路和TGF-β信号通路的下调外,还涉及补体系统的变化.泪腺良性淋巴上皮病变的发生和发展是多种基因和通路共同作用的结果.

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  • 来源
    《中华实验眼科杂志》 |2016年第10期|878-882|共5页
  • 作者

    李静; 葛心; 马建民; 王霄娜; 刘骁;

  • 作者单位

    100730北京,首都医科大学附属北京同仁医院北京同仁眼科中心 北京市眼科研究所 北京市眼科学与视觉科学重点实验室;

    100730北京,首都医科大学附属北京同仁医院北京同仁眼科中心 北京市眼科研究所 北京市眼科学与视觉科学重点实验室;

    100730北京,首都医科大学附属北京同仁医院北京同仁眼科中心 北京市眼科研究所 北京市眼科学与视觉科学重点实验室;

    100730北京,首都医科大学附属北京同仁医院北京同仁眼科中心 北京市眼科研究所 北京市眼科学与视觉科学重点实验室;

    100730北京,首都医科大学附属北京同仁医院北京同仁眼科中心 北京市眼科研究所 北京市眼科学与视觉科学重点实验室;

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    泪腺良性淋巴上皮病变; 眼眶海绵状血管瘤; 微阵列芯片; 基因表达谱; 发病机制; 聚合酶链反应;

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