Population-Based Study Reveals New Risk-Stratification Biomarker Panel for Barrett's Esophagus
Population-Based Study Reveals New Risk-Stratification Biomarker Panel for Barrett's Esophagus
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DOI：
10.1053/j.gastro.2012.06.041
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发表时间：
2012-10-01
期刊：
影响因子：
29.4
通讯作者：
Fitzgerald, Rebecca C.
中科院分区：
文献类型：
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作者：
Bird-Lieberman, Elizabeth L.;Dunn, Jason M.;Fitzgerald, Rebecca C.
背景与目的：Barrett食管（BE）进展为食管腺癌（EAC）的风险较低且难以计算。需要有确定风险的准确工具，以优化监测和干预。我们评估了候选生物标志物预测哪些BE病例将进展为EAC或高度异型增生的能力，并确定了那些可以在福尔马林固定组织中测量的生物标志物。方法：我们分析了一项巢式病例对照研究的数据，该研究使用了基于人群的北方爱尔兰BE登记（1993-2005）。在诊断为BE后>6个月进展为EAC（n = 89）或高度异型增生的病例与对照组（非进展者，n = 291）在年龄、性别和BE诊断年份方面相匹配。在首次诊断为BE的患者的石蜡包埋组织样本中评估了已确定的生物标志物（异常DNA含量、p53和细胞周期蛋白A表达）和新生物标志物（唾液酸刘易斯（a）、刘易斯（x）和米曲霉凝集素[AOL]的水平以及麦胚凝集素的结合）。基于生物标志物状态，应用条件logistic回归分析评估异型增生和非异型增生BE患者的进展几率。结果：除刘易斯（x）外，低度异型增生和所有检测的生物标志物均与EAC或高度异型增生的风险相关。在向后选择中，包括低度异型增生、异常DNA倍性和AOL的组最准确地鉴定了进展者和非进展者。对于每种额外的生物标志物，伴有低度异型增生的BE患者进展的校正比值比为3.74（95%置信区间，2.43-5.79），对于无异型增生的患者，每种额外因素的风险增加2.99（95%置信区间，1.72-5.20）。结论：低度异型增生、异常DNA倍体和AOL可用于鉴别最有可能发展为EAC或高度异型增生的BE患者。
BACKGROUND & AIMS: The risk of progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is low and difficult to calculate. Accurate tools to determine risk are needed to optimize surveillance and intervention. We assessed the ability of candidate biomarkers to predict which cases of BE will progress to EAC or high-grade dysplasia and identified those that can be measured in formalin-fixed tissues. METHODS: We analyzed data from a nested case-control study performed using the population-based Northern Ireland BE Register (1993-2005). Cases who progressed to EAC (n = 89) or high-grade dysplasia >6 months after diagnosis with BE were matched to controls (nonprogressors, n = 291), for age, sex, and year of BE diagnosis. Established biomarkers (abnormal DNA content, p53, and cyclin A expression) and new biomarkers (levels of sialyl Lewis(a), Lewis(x), and Aspergillus oryzae lectin [AOL] and binding of wheat germ agglutinin) were assessed in paraffin-embedded tissue samples from patients with a first diagnosis of BE. Conditional logistic regression analysis was applied to assess odds of progression for patients with dysplastic and nondysplastic BE, based on biomarker status. RESULTS: Low-grade dysplasia and all biomarkers tested, other than Lewis(x), were associated with risk of EAC or high-grade dysplasia. In backward selection, a panel comprising low-grade dysplasia, abnormal DNA ploidy, and AOL most accurately identified progressors and nonprogressors. The adjusted odds ratio for progression of patients with BE with low-grade dysplasia was 3.74 (95% confidence interval, 2.43-5.79) for each additional biomarker and the risk increased by 2.99 for each additional factor (95% confidence interval, 1.72-5.20) in patients without dysplasia. CONCLUSIONS: Low-grade dysplasia, abnormal DNA ploidy, and AOL can be used to identify patients with BE most likely to develop EAC or high-grade dysplasia.