Groome Maximillian, Lindsay Jamie, Ross Peter E, Cotton James P, Hupp Ted R, Dillon John F
Gut Group, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK.
Eur J Gastroenterol Hepatol. 2008 Oct;20(10):961-5. doi: 10.1097/MEG.0b013e3282ffd9bd.
Oesophageal adenocarcinoma is an increasingly common diagnosis and cause of death; risk factors include 'Barrett's epithelium' (BE). Endoscopic surveillance is most commonly used but is expensive. Other methods of surveillance have been suggested including nonendoscopic balloon cytology, but are handicapped by relying on cytological techniques; hence the need for a partner technology such as a biomarker. From earlier work we know the most commonly expressed oesophageal stress response proteins are SEP 53, SEP70 and anterior gradient-2 (AG-2). We set out to map the expression of these stress response proteins and explore their potential as prototype biomarkers of BE.
Patients (n=192) presenting to the endoscopy unit of a large teaching hospital with symptoms of gastro-oesophageal reflux disease or a known BE were recruited, endoscopically examined and the biopsies obtained were examined for heat shock protein expression.
Normal controls and those with oesophagitis predominantly expressed SEP 53 (76.9/91.95%) and SEP 70 (79.48/89.65%). Although those with BE expressed AG-2; using this expression as a marker for BE, gives a sensitivity of 65.15% and specificity of 89.68% (positive predictive value of 76.78% and negative predictive value of 84.9%) and in gastro-oesophageal reflux disease a sensitivity of 65.15% and specificity of 90.80% (positive predictive value of 84.31% and negative predictive value of 77.45%). We confirmed that AG-2 is preferentially expressed in BE; suggesting its use would allow a screening tool with specificity of around 90%.
食管腺癌是一种日益常见的诊断疾病和死亡原因;风险因素包括“巴雷特食管上皮”(BE)。内镜监测是最常用的方法,但费用高昂。有人提出了其他监测方法,包括非内镜下球囊细胞学检查,但这些方法因依赖细胞学技术而受到限制;因此需要一种如生物标志物这样的辅助技术。从早期的研究中我们了解到,最常表达的食管应激反应蛋白是SEP 53、SEP70和前梯度蛋白-2(AG-2)。我们着手绘制这些应激反应蛋白的表达图谱,并探索它们作为BE原型生物标志物的潜力。
招募了192名到一家大型教学医院内镜科就诊、有胃食管反流病症状或已知患有BE的患者,进行内镜检查,并对获取的活检组织进行热休克蛋白表达检测。
正常对照组和食管炎患者主要表达SEP 53(76.9/91.95%)和SEP 70(79.48/89.65%)。虽然BE患者表达AG-2;以这种表达作为BE的标志物,其敏感性为65.15%,特异性为89.68%(阳性预测值为76.78%,阴性预测值为84.9%),在胃食管反流病中敏感性为65.15%,特异性为90.80%(阳性预测值为84.31%,阴性预测值为77.45%)。我们证实AG-2在BE中优先表达;这表明使用它可以得到一种特异性约为90%的筛查工具。