目的鉴定胆管癌(cholangiocarcinoma,CCA)甲基化与表达谱综合生物标志物,预测CCA患者预后。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)下载33例CCA样本和8例正常样本基因组甲基化数据及临床信息表达谱数据,同时从基因表达综...目的鉴定胆管癌(cholangiocarcinoma,CCA)甲基化与表达谱综合生物标志物,预测CCA患者预后。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)下载33例CCA样本和8例正常样本基因组甲基化数据及临床信息表达谱数据,同时从基因表达综合数据库(Gene Expression Omnibus,GEO)下载甲基化数据进行验证。鉴定差异甲基化基因(DMGs)与差异表达基因(DEGs)的交集基因,采用Cox比例风险回归模型鉴定甲基化生物标志物,并使用ROC曲线来评估该模型的性能。在验证组中对该模型进行验证,通过GO功能注释,探讨DNA甲基化标志物的生物学功能。结果通过对TCGA甲基化数据分析,共鉴定出600个差异甲基化基因和6876个差异表达基因,并从中筛选出与生存相关的2个甲基化基因(SOX9和FZD10),最终将SOX9和FZD10组合基因构建预后预测模型,作为CCA预后的生物标志物。ROC曲线下面积(AUC)为0.90。SOX9和FZD10组合生物标志物能够将CCA患者区分为高风险组和低风险组,低风险组患者总生存期明显高于高风险组(2.07年vs 0.92年)。多因素Cox回归分析表明,SOX9和FZD10组合生物标志物是CCA患者预后的独立预测因子。基因本体(GO)功能分析表明,SOX9和FZD10参与转录因子、转录调控、肿瘤蛋白多糖调节和干细胞的调控。结论本研究经过多组学分析,在TCGA数据中筛选出SOX9和FZD10基因组合的甲基化预后标志物,可以将CCA患者分为高风险组与低风险组,并且该组合基因是CCA独立的预后预测因子。展开更多
The cattle different stage embryos obtained from in vitro was studied using the technology of single preimplantation embryo mRNA different display:single 8-cell and blastocyst stage embryos were studied using technolo...The cattle different stage embryos obtained from in vitro was studied using the technology of single preimplantation embryo mRNA different display:single 8-cell and blastocyst stage embryos were studied using technology of mRNA different display and one different fragment was found. The result suggested that this fragment displayed high homology (99%) to cattle mRNA for ribosomal protein L31. Then to detect the expression of RPL31mRNA in 8 cell and blastocyst stage embryos by real-time quantitative PCR,the result showed the relative amount of 8 cells was 3.2 times of blastocyst's.展开更多
基金Supported by National "863" Project (2008AA101007)~~
文摘The cattle different stage embryos obtained from in vitro was studied using the technology of single preimplantation embryo mRNA different display:single 8-cell and blastocyst stage embryos were studied using technology of mRNA different display and one different fragment was found. The result suggested that this fragment displayed high homology (99%) to cattle mRNA for ribosomal protein L31. Then to detect the expression of RPL31mRNA in 8 cell and blastocyst stage embryos by real-time quantitative PCR,the result showed the relative amount of 8 cells was 3.2 times of blastocyst's.