CAJ | 학술논문

背景人葡萄膜黑色素瘤(UM)组织与正常组织中存在差异表达基因,但国外不同文献报道的结果不尽一致,而国内对人UM基因表达的改变及其相关的作用通路的研究较少. 目的应用基因芯片技术探讨人UM中差异表达的基因,分析差异基因参与的重要信号通路. 方法收集在北京同仁医院因原发性UM行眼球摘除并经组织病理学证实为梭形细胞型UM的组织标本4例,以正常供体葡萄膜组织作为对照组.利用Human Genome U133 Plus 2.0芯片技术筛查2种组织中基因表达的差异,并使用GOEAST富集分析软件对差异基因的重要生物学功能及参与的通路进行分析.结果与正常的葡萄膜组织对比,人UM中有4 165个差异基因,占12.50％,其中包含1 236个上调基因和2 929个下调基因,分别占3.71％和8.79％.人UM组织中上调5倍或以上基因为113个,下调50％的基因为1 053个;上调10倍或以上的基因为21个,下调90％或以上的基因为422个;上调50倍或以上的基因为1个,下调98％或以上的基因为33个;上调100倍或以上的基因为1个,下调99％或以上的基因为5个.按功能学分类表明,差异表达基因中包括细胞分化与增生基因、发育相关基因、细胞黏附相关基因、免疫应答基因、调节转录基因、信号转导相关基因、凋亡以及抗凋亡相关基因等;差异表达基因参与的代谢通路涉及血管形成过程的代谢通路、细胞周期相关的蛋白激酶通路以及B淋巴细胞或T淋巴细胞的代谢通路等. 结论人UM组织与正常人葡萄膜组织中基因表达谱明显不同,这些差异表达的基因除参与血管生成、激酶通路等已知的UM发育有关的代谢通路外,还涉及免疫系统的变化.人UM的发生和进展是多种基因、多种通路共同作用的结果.
배경 인포도막흑색소류(UM)조직여정상조직중존재차이표체기인,단국외불동문헌보도적결과불진일치,이국내대인UM기인표체적개변급기상관적작용통로적연구교소. 목적 응용기인심편기술탐토인UM중차이표체적기인,분석차이기인삼여적중요신호통로. 방법 수집재북경동인의원인원발성UM행안구적제병경조직병이학증실위사형세포형UM적조직표본4례,이정상공체포도막조직작위대조조.이용Human Genome U133 Plus 2.0심편기술사사2충조직중기인표체적차이,병사용GOEAST부집분석연건대차이기인적중요생물학공능급삼여적통로진행분석.결과 여정상적포도막조직대비,인UM중유4 165개차이기인,점12.50％,기중포함1 236개상조기인화2 929개하조기인,분별점3.71％화8.79％.인UM조직중상조5배혹이상기인위113개,하조50％적기인위1 053개;상조10배혹이상적기인위21개,하조90％혹이상적기인위422개;상조50배혹이상적기인위1개,하조98％혹이상적기인위33개;상조100배혹이상적기인위1개,하조99％혹이상적기인위5개.안공능학분류표명,차이표체기인중포괄세포분화여증생기인、발육상관기인、세포점부상관기인、면역응답기인、조절전록기인、신호전도상관기인、조망이급항조망상관기인등;차이표체기인삼여적대사통로섭급혈관형성과정적대사통로、세포주기상관적단백격매통로이급B림파세포혹T림파세포적대사통로등. 결론 인UM조직여정상인포도막조직중기인표체보명현불동,저사차이표체적기인제삼여혈관생성、격매통로등이지적UM발육유관적대사통로외,환섭급면역계통적변화.인UM적발생화진전시다충기인、다충통로공동작용적결과.
Background Studies showed that there exsits differential gene expression in human uveal melanoma (UM).However, the researching results are somewhat inconsistently abroad, while relevant literature is still less in China.Few domestic researches have reported the abnormalities of gene transcription level or the pathways of these genes.Objective This study was to compare the gene expression profiles between human UM and normal uvea tissues and analyze the metabolic pathways involved in these differentially expressed genes.Methods Four human UM samples were collected in Beijing Tongren Eye Center,and 4 pieces of normal uveal tissues from 4 donors served as controls.The expression of genes was detected with Human Genome U133 Plus 2.0 chip,and the expression profiles were compared between two groups.The biological functions and active pathways of the genes were analyzed by Gene Ontology Enrichment Analysis Software Toolkit (GOEAST).Results Compared with the normal controls,4 165 differential genes were screened in human UM (12.50％) ,including 1 236 up-regulated genes (3.71％) and 2 929 down-regulated genes (8.79％) ,in which the genes of raised more than 5-, 10-,50-and 100-fold were 113,21,1 and 1, respectively, and the genes of reduced by 50％ ,90％ ,98％ and 99％ were 1 053,422,33 and 5,respectively.The functions of these differentially expressed genes were associated with cellular differentiation and growth,development, cell adhension, immun response, transcriptional contol, signal transduction and anti-apoptosis.The metabolic pathways of differentially expressed genes included angiogenesis pathway, cell-cycle related protein kinase pathway and immune regulatory pathway (involving B lymphocytes and T lymphocytes).Conclusions Gene expression profiles are evidently different between human UM and normal uveal tissue.The variation of the gene profiles in human UM leads to the changes of multiple biological functions including angiogenesis and kinase pathway even immun system.It is implied that the pathogenesis of human UM is a comprehensive effect of multiple genes and biological pathways.