Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma.
Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma.
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DOI：
10.1371/journal.pone.0022513
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Study of Digestive Health
中科院分区：
文献类型：
--
作者：
Nancarrow DJ;Clouston AD;Smithers BM;Gotley DC;Drew PA;Watson DI;Tyagi S;Hayward NK;Whiteman DC;Australian Cancer Study;Study of Digestive Health
食管腺癌(EAC)由于发病率的快速上升和非常低的存活率，已经成为西方国家的一个主要问题。这种癌症发生的关键危险因素之一是Barrett‘s食道(BE)的存在，据信它是对反复胃食道反流的反应而形成的。在这项研究中，我们对食道活检组织提取的总RNA进行了比较的全基因组表达谱分析(使用Illumina全基因组珠阵列)，这些总RNA来自EAC、BE(在没有EAC的情况下)和那些具有正常鳞状上皮的人。我们将这些数据与来自三个类似研究的可公开获取的原始数据相结合，以研究这三个组织状态之间的关键基因和本体差异。这一结果支持了BE是一种具有增强的糖蛋白合成机制(DPP4、ATP2A3、AGR2)的组织的推断，旨在提供针对胃食道反流的强大的粘膜防御。EAC表现出侵袭性癌症中预期的增强的细胞外基质重塑(胶原蛋白、IGFBP7、PLAU)作用，以及与粘膜(MUC6、CA2、TFF1)和异源(AKR1C2、AKR1B10)防御相关的基因表达减少的证据。当我们的结果与以前的全基因组表达谱研究相比较时，角蛋白、粘蛋白、膜联蛋白和三叶因子基因组是最常见的差异表达基因家族。这里确定的11个基因也出现在至少3个其他的图谱研究中。我们使用这些基因在两个最大的队列中区分鳞状上皮、BE和EAC，使用支持向量机进行留一交叉验证(LOOCV)分析。虽然这种方法在区分鳞状上皮和BE方面是令人满意的，但它表明有必要对BE和EAC之间的轮廓变化进行更详细的研究。
Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.
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影响因子：
4.8
作者：
Fox, CA;Sapinoso, LM;Powell, SM
通讯作者：
Powell, SM
影响因子：
11.5
作者：
Helm, J;Enkemann, SA;Yeatman, TJ
通讯作者：
Yeatman, TJ
影响因子：
9.8
作者：
Dixon, J;Strugala, V;Pearson, JP
通讯作者：
Pearson, JP
Barrett食管和食管腺癌中染色体畸变的全基因组分类：高密度的单核苷酸多态性阵列分析。
DOI：
10.1158/1940-6207.capr-09-0265
发表时间：
2010-09
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Gu J;Ajani JA;Hawk ET;Ye Y;Lee JH;Bhutani MS;Hofstetter WL;Swisher SG;Wang KK;Wu X
通讯作者：
Wu X
影响因子：
14.9
作者：
Bruford, Elspeth A.;Lush, Michael J.;Wright, Mathew W.;Sneddon, Tam P.;Povey, Sue;Birney, Ewan
通讯作者：
Birney, Ewan