Goblet Cell Ratio in Combination with Differentiation and Stem Cell Markers in Barrett Esophagus Allow Distinction of Patients with and without Esophageal Adenocarcinoma.
Goblet Cell Ratio in Combination with Differentiation and Stem Cell Markers in Barrett Esophagus Allow Distinction of Patients with and without Esophageal Adenocarcinoma.
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DOI：
10.1158/1940-6207.capr-16-0117
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Quante M
中科院分区：
文献类型：
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作者：
Schellnegger R;Quante A;Rospleszcz S;Schernhammer M;Höhl B;Tobiasch M;Pastula A;Brandtner A;Abrams JA;Strauch K;Schmid RM;Vieth M;Wang TC;Quante M
食管腺癌（EAC）发病率的上升反映在巴雷特食管（BE）患病率的上升，这是一种导致大量个体处于这种致命恶性肿瘤“风险”的前驱病变。在BE患者中，每年只有约0.3%的患者会发展为EAC。由于大量的患者进行内镜监测，有必要在不断增长的BE患者人群中进行风险预测。我们从Barrett食管的炎症（IL-1β）依赖性小鼠模型中鉴定了4种潜在的生物标志物，并在189名患有和不患有HGD/早期癌症（T1）的BE患者中进行了测试。主要目的是区分无发育不良证据的BE患者和发育不良患者。增加的干细胞标志物LGR 5和小生境细胞标志物DCLK 1以及减少的分化标志物（分泌性粘液细胞，TFF 2+细胞）与小鼠中升高的肿瘤评分相关。在概述了BE小鼠模型中这些标志物的起源后，我们显示了对人类BE的适用性：我们将96例非异型增生BE组织患者与97例BE和HGD或早期癌症患者进行了比较。低水平的TFF 2（AUC 87.2%）提供了非异型增生BE和患有癌症的BE之间的最佳区分，其次是高水平的DCLK 1（AUC 83.4%）、低GC比率（AUC 79.4%）和高LGR 5（AUC 71.4%）。GC的比例，而不是GC本身的存在，被认为是一个重要的因素。这些发现可能有助于开发未来BE患者的风险预测模型，并最终改善EAC监测。
The rising incidence of esophageal adenocarcinoma (EAC) is mirrored by the increasing prevalence of Barrett’s Esophagus (BE), a precursor lesion resulting in a large number of individuals “at risk” for this lethal malignancy. Among BE patients only ~0.3% annually will develop EAC. Since large numbers of patients are followed in endoscopic surveillance, there is a need for risk prediction among a growing population of BE patients. We identified 4 potential biomarkers from an inflammation (IL-1β)-dependent mouse model of Barrett’s esophagus and tested them in 189 BE patients with and without HGD/early cancer (T1). The primary goal was to distinguish BE patients with no evidence of dysplasia from those with dysplasia. Increasing stem cell marker LGR5 and niche cell marker DCLK1 and decreasing differentiation marker (secretory mucus cells, TFF2+ cells) correlated with elevated tumor score in the mouse. Having outlined the origin of those markers in the BE mouse model we showed the applicability for human BE: We compared 96 patients with non-dysplastic BE tissue to 97 patients with BE and HGD or early cancer. Low levels of TFF2 (AUC 87.2%) provided the best discrimination between non-dysplastic BE and BE with cancer, followed by high levels of DCLK1 (AUC 83.4%), low GC ratio (AUC 79.4%) and high LGR5 (AUC 71.4%). The GC ratio, rather than the presence of GCs per se, was found to be an important discriminator. These findings may be useful in developing future risk prediction models for BE patients and ultimately to improve EAC surveillance.