The establishment of gene expression profiling-guided clinical precision treatment for patients with endometrial carcinoma
首发时间:2017-05-16
Abstract:Endometrial carcinoma (EC) is a common gynaecologic cancer. Most EC patients, especially those with early stage endometrioid endometrial adenocarcinoma (EEC), will have a good prognosis. Studies showed that similar staging and histology results in early stage EC patients had completely different prognoses postoperatively. EC is a highly heterogeneous disease, and different genetic alterations may exist in the same histological phenotype of carcinoma, indicating that some flaws exist in the current therapy strategy based on the clinical pathological classification and Bokhman's classification. It's necessary to establish new molecular type of the EC. 492 EC-related genes from the NCBI database were selected, and oligoprobes were then designed with the UniGene Database and the Human Reference Sequence (RefSeq) Database. An EC-related, 492-gene microarray was constructed with the oligoprobes. A hierarchical cluster algorithm was used to sort tumour samples according to gene expression patterns. Significance analysis of microarrays (SAM) was used to select the different expressed genes. Genes' expression were tested by immunohistochemistry assay. Results showed that the UPSC samples exhibited distinct gene expression profiles compared to those of EEC and 46 genes that could highly discriminate UPSC from EEC. 21 genes were selected and defined as EC prognosis-related genes and some of the genes. Our data suggests seeking new molecular type of the EC different from the traditional clinical pathological classification and Bokhman's classification, will help in the accurate prognosis and practice of precise therapy of EC.?????
keywords: endometrioid adenocarcinoma molecular typing gene expression profiling DUSP1
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基因表达谱介导的子宫内膜癌临床精准治疗的建立
摘要:子宫内膜癌是一种常见的妇科疾,许多早期子宫内膜癌,尤其是子宫内膜样腺癌预后较好。研究表明存在一些分期及组织学特征相同的早期子宫内膜癌患者其术后预后有差别。子宫内膜癌是一种高度异质性疾病,并且不同遗传变异可能存在与相同组织学表型的内膜癌灶中,这表明基于当前临床病理分类和Bokhman的分类的治疗策略存在一些缺陷,因此建立一个新的子宫内膜癌的分子分型显得十分重要。我们从NCBI数据库挑选了492个子宫内膜癌相关基因,根据UniGene 及RefSeq数据库设计了寡核苷酸探针,从而构建了一种包含492个子宫内膜癌相关的基因芯片。根据基因表达模式,采用层次聚类算法对肿瘤样本进行分类。采用SAM方法挑选差异表达基因。免疫组化法检测基因表达。研究结果表明子宫浆液性乳头状癌与子宫内膜样腺癌相比较,有着特定的基因表达谱,两者相比共有46个差异表达基因。共挑选出21个与子宫内膜癌预后相关的基因。本研究数据表明,探寻与传统子宫内膜癌临床病理及Bokhman分类不同的新的分子分型,有助于准确判断子宫内膜癌预后及有助于子宫内膜癌精准治疗。
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