Increased c-myb mRNA expression in Barrett's esophagus and Barrett's-associated adenocarcinoma
Increased c-myb mRNA expression in Barrett's esophagus and Barrett's-associated adenocarcinoma
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DOI：
10.1006/jsre.2001.6186
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发表时间：
2001-08-01
影响因子：
2.2
通讯作者：
Danenberg, PV
中科院分区：
文献类型：
--
作者：
Brabender, J;Lord, RV;Danenberg, PV
背景资料。食管腺癌的发展经历了一个多阶段的过程，其组织病理学特征是从Barrett肠化生发展到Barrett食管伴不典型增生，最终发展为腺癌。这个过程的遗传学基础越来越清楚，但还没有研究检验转录因子c-myb在这种疾病中的作用。材料和方法。应用定量逆转录聚合酶链式反应(RT-PCR)方法检测16例Barrett肠化生和腺癌组织中c-myb基因的表达水平。22例，与正常鳞状食道组织匹配38例，非Barrett‘s食道或慢性胃食道反流病患者的正常鳞状食道组织10例。Barrett肠上皮化生组织中c-MYB基因表达水平显著高于正常食管组(P=0.013)，Barrett相关腺癌组织中c-MYB基因表达水平高于正常食管鳞状组织(P=0.001)。C-myb的表达在组织学分级较差的组织中逐渐升高，从正常鳞状上皮到Barrett肠化生，从Barrett肠化生到食管腺癌(P=0.002)。癌组织中c-myb的表达水平也显著高于非癌组(P<；0.001)和无Barrett‘s食道或胃食道反流病证据的对照组(P=0.003)。C-MYB基因只有在癌症患者中有很高的表达水平。这些结果提示c-myb基因表达上调是Barrett‘s食管腺癌及相关腺癌发生的早期事件，c-myb基因高表达可能是临床上检测隐匿性腺癌的一个有用的生物标志物，Barrett相关腺癌患者的食道存在广泛的癌“野”效应。(C)2001年学术出版社。
Background. Esophageal adenocarcinoma develops through a multistage process which is characterized histopathologically by progression from Barrett's intestinal metaplasia to Barrett's esophagus with dysplasia and ultimately to adenocarcinoma. The genetic basis of this process is increasingly well understood, but no studies have examined the role of the transcription factor c-myb in this disease.Material and methods. c-myb mRNA expression levels were measured using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method in specimens of Barrett's intestinal metaplasia (n = 16), adenocarcinoma. (n = 22), matching normal squamous esophagus tissues (n = 38), and normal squamous esophagus tissues from patients without Barrett's esophagus or chronic gastroesophageal reflux disease (n = 10).Results. The median c-myb mRNA expression levels were significantly increased in Barrett's intestinal metaplasia tissues compared to normal esophagus tissues (P = 0.013) and in Barrett's-associated adenocarcinoma tissues compared to normal squamous esophagus tissues (P = 0.001). The c-myb expression levels increased progressively and significantly in histopathologically worse tissue types, with an increase from normal squamous esophagus mucosa to Barrett's intestinal metaplasia, and from Barrett's intestinal metaplasia to adenocarcinoma of the esophagus (P = 0.002). Median c-myb expression levels were also significantly higher in histologically normal squamous esophagus tissues from cancer patients compared to normal esophagus tissues from patients without cancer (P < 0.001) and a control group without evidence of Barrett's esophagus or gastroesophageal reflux disease (P = 0.003). Very high c-myb mRNA expression levels were found only in patients with cancer.Conclusion. These findings suggest that upregulation of c-myb mRNA expression is an early event in the development of Barrett's esophagus and associated adenocarcinoma, that high c-myb mRNA expression levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients with Barrett's-associated adenocarcinoma. (C) 2001 Academic Press.