Hamoui Nahid, Peters Jeffrey H, Schneider Sylke, Uchida Kazumi, Yang Dongyun, Vallböhmer Daniel, Hagen Jeffrey A, DeMeester Steven R, DeMeester Tom R, Danenberg Kathleen, Danenberg Peter
Department of Surgery, Division of Thoracic and Foregut Surgery, University of Southern California, Los Angeles 90033, USA.
Arch Surg. 2004 Jul;139(7):712-6; discussion 716-7. doi: 10.1001/archsurg.139.7.712.
Although genetic changes associated with the progression to Barrett esophagus and adenocarcinoma have been identified, changes in gene expression associated with gastroesophageal reflux disease have not been reported. We examined expression levels of several genes important in carcinogenesis and compared expression levels with alterations in esophageal acid exposure.
PATIENTS, DESIGN, AND SETTING: Prospective analysis of 61 patients initially seen with reflux symptoms at a private academic hospital.
Paired esophageal biopsy specimens of squamous epithelium 3 cm above the squamocolumnar junction. All patients had 24-hour pH monitoring performed.
Cyclooxygenase (COX) 1, COX-2, thymidylate synthase, human telomerase reverse transcriptase (hTERT), Bcl-2 protein, survivin protein, secreted protein acidic and rich in cysteine (SPARC), tetraspan (TSPAN), and caudal-type homeobox transcription factor 2 (CDX2) messenger RNA expression analysis was performed on snap-frozen, microdissected tissue using a quantitative reverse transcriptase-polymerase chain reaction method. Linear regression and the Pearson product moment correlation were used to relate gene expression to parameters of the 24-hour pH record.
Expression levels of COX-2 correlated positively with the 24-hour pH score (r = 0.25, P =.05). There was no correlation between the expression of other tested genes and esophageal acid exposure. There was also no significant increase in COX-2 expression in patients with esophagitis or in those who used nonsteroidal anti-inflammatory drugs.
To our knowledge, these data provide among the first reported correlation of genetic changes and increased esophageal acid exposure in patients with gastroesophageal reflux symptoms. The changes in gene expression occur before any metaplastic changes in the tissue are apparent, and may in the future be useful in predicting which patients will progress through a metaplasia-dysplasia carcinoma sequence.
尽管已确定与巴雷特食管和腺癌进展相关的基因变化，但与胃食管反流病相关的基因表达变化尚未见报道。我们检测了几种在致癌过程中起重要作用的基因的表达水平，并将其表达水平与食管酸暴露的改变进行了比较。
患者、设计与研究地点：对一家私立学术医院最初因反流症状就诊的61例患者进行前瞻性分析。
在鳞柱状上皮交界处上方3厘米处获取成对的食管鳞状上皮活检标本。所有患者均进行了24小时pH监测。
使用定量逆转录聚合酶链反应方法，对快速冷冻、显微切割的组织进行环氧合酶（COX）1、COX-2、胸苷酸合成酶、人端粒酶逆转录酶（hTERT）、Bcl-2蛋白、生存素蛋白、富含半胱氨酸的酸性分泌蛋白（SPARC）、四跨膜蛋白（TSPAN）和尾型同源盒转录因子2（CDX2）信使核糖核酸表达分析。采用线性回归和Pearson积矩相关分析将基因表达与24小时pH记录参数相关联。
COX-2的表达水平与24小时pH评分呈正相关（r = 0.25，P = 0.05）。其他检测基因的表达与食管酸暴露之间无相关性。食管炎患者或使用非甾体抗炎药的患者中，COX-2的表达也没有显著增加。
据我们所知，这些数据首次报道了胃食管反流症状患者基因变化与食管酸暴露增加之间的相关性。基因表达的变化在组织出现任何化生变化之前就已发生，未来可能有助于预测哪些患者会经历化生-发育异常-癌序列。
