机构地区:[1]生物芯片上海国家工程研究中心,201203 [2]上海交通大学医学院附属新华医院消化内科 [3]上海交通大学医学院附属瑞金医院消化内科
出 处:《胃肠病学》2006年第10期581-585,共5页Chinese Journal of Gastroenterology
基 金:国家高科技"863"项目(No.2002AA2Z2002);上海市科委优秀学科带头人(No.05XDB1414);上海交通大学医学院骨干教师基金项目资助
摘 要:背景:基因芯片等高通量的研究手段已在肿瘤研究中得到广泛的应用,胃癌方面的研究主要集中在手术切除标本,对胃镜下取得的疑似胃癌组织的基因表达比较研究则较少报道。目的:比较胃镜下取得的病理诊断为胃癌和非癌样品的基因表达谱特征,为识别胃癌早期诊断的指标和疾病的分子分型奠定基础。方法:内镜下取47例胃癌疑似病变组织和对应非病变组织,经病理学诊断为胃癌28例,非癌病变19例。提取RNA,采用含14592个点的人cDNA芯片,经RNA放大技术进行基因表达谱的检测,检测结果采用GeneSpring软件分析,数据标准化用局部加权回归分析(LOWESS)处理,胃癌和非癌两组样品的组内和组间差异的显著性分析应用差异显著性分析(SAM)方法。结果:以30%样品中的表达调节水平大于1.5倍作为差异基因筛选标准,胃癌组表达上调的基因有133个,下调的有143个。非胃癌样品中有51个基因表达上调,22个表达下调,其中分别有18个上调基因和13个下调基因与胃癌组相同。组间差异分析筛选出40个基因,其表达调节可以由之进行胃癌和非癌组样品的区分。结论:基因表达谱芯片技术可以有效地应用于识别胃癌和非癌样品中的差异表达基因,并可用于肿瘤发病机制和分子分型的研究。Background: Gene microarray, along with other high throughout technology, has been widely used in the research of cancer. Most of the investigations on gastric cancer were based on samples obtained during surgical operation, only few studies were based on samples obtained endoscopically. Aims: To compare the gene expression profile of pathologically confirmed gastric cancer and non-cancer samples obtained endoscopically with the hope to identify biomarkers for early diagnosis and molecular subtyping of gastric cancer. Methods: Tissue samples of suspected gastric cancer lesion and contra-lateral non-cancerous lesion were obtained endoscopically in 47 patients with suspected gastric cancer. Of these 47 patients, 28 were confirmed pathologically to be gastric cancer and 19 non-cancer. RNA was extracted, amplified and gene expression profile was determined by cDNA microarray covering 14 592 spots prepared by our laboratory. The data obtained were analyzed with GeneSpring software and normalized with locally weighted linear regression (LOWESS). The significance of intergroup and intragroup differences between cancer and non-cancer samples was analyzed by significance analysis of microarray (SAM). Results: Using expression regulating level higher than 1.5 fold in more than 30% of the samples as the criteria of discriminating gene, 133 genes were up-regulated and 143 genes were down-regulated in gastric cancer sample group, and 51 genes were up-regulated and 22 genes were down-regulated in non-cancer sample group. Among them, 18 up-regulated genes and 13 down-regulated genes were overlaped between gastric cancer and non-cancer sample groups. Analysis of intergroup differences showed that the regulating expression of 40 genes could be used for the differentiation between gastric cancer and non-cancer samples. Conclusions: Gene expression profile microarray determination technique can be used effectively for the detection of discriminating genes between gastric cancer and noncancer samples, and can be us
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