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食管腺癌中的微小RNA:功能意义及新型分子疾病标志物开发潜力

MicroRNAs in Esophageal Adenocarcinoma: Functional Significance and Potential for the Development of New Molecular Disease Markers.

作者信息

Bobryshev Yuri V, Orekhov Alexander N, Chistiakov Dmitry A

机构信息

Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.

出版信息

Curr Pharm Des. 2015;21(23):3402-16. doi: 10.2174/1381612821666150311124418.

Abstract

Esophageal adenocarcinoma (EAC) originates from the neoplastic changes in the esophageal epithelium. Barrett's esophagus (BE) precedes EAC. In BE metaplasia, the normal stratified squamous epithelium is replaced by the intestinal columnar epithelium. Esophageal metaplasia might further progress to dysplasia, neoplasia, and EAC. The neoplastic progression from BE to EAC is accompanied with marked histological and molecular changes including deregulation of key signaling pathways and expression of various genes including microRNA (miRNA). To date, stable and progressive changes in expression levels of different miRNA subsets are shown for each stage of EAC carcinogenesis. This suggests that miRNAs might become promising markers for BE/EAC diagnosis and prognosis of survival of EAC patients and lymph node tumor metastases. Development of new molecular markers based on the assessment of miRNAs circulating in patients' biofluids would improve the effectiveness and cost-effectiveness of esophageal cancer surveillance regimens and open new possibilities for high throughput screening programs to identify BE patients who are at high-risk for the development of highgrade dysplasia or progression to EAC.

摘要

食管腺癌(EAC)起源于食管上皮的肿瘤性变化。巴雷特食管(BE)先于EAC出现。在BE化生过程中,正常的复层鳞状上皮被肠柱状上皮所取代。食管化生可能会进一步发展为发育异常、肿瘤形成以及EAC。从BE到EAC的肿瘤进展伴随着显著的组织学和分子变化,包括关键信号通路的失调以及各种基因(包括微小RNA(miRNA))的表达。迄今为止,EAC致癌作用的每个阶段都显示出不同miRNA亚群表达水平的稳定和渐进性变化。这表明miRNA可能成为BE/EAC诊断以及EAC患者生存预后和淋巴结肿瘤转移的有前景的标志物。基于对患者生物流体中循环miRNA的评估开发新的分子标志物,将提高食管癌监测方案的有效性和成本效益,并为高通量筛查项目开辟新的可能性,以识别有发生高级别发育异常或进展为EAC高风险的BE患者。

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