Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features.
Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features.
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使用表观遗传学和临床特征预测巴雷特食管进展的三层风险分层模型。
DOI：
10.1371/journal.pone.0001890
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发表时间：
2008-04-02
期刊：
影响因子：
3.7
通讯作者：
Meltzer SJ
中科院分区：
文献类型：
--
作者：
Sato F;Jin Z;Schulmann K;Wang J;Greenwald BD;Ito T;Kan T;Hamilton JP;Yang J;Paun B;David S;Olaru A;Cheng Y;Mori Y;Abraham JM;Yfantis HG;Wu TT;Fredericksen MB;Wang KK;Canto M;Romero Y;Feng Z;Meltzer SJ
Barrett‘s食道易患食管腺癌。然而，由于Barrett‘s食管腺癌的发生率较低，因此对Barrett’s食管镜检查的价值一直存在争议。此外，在异型增生的组织学分期中，观察者间的高度差异和采样依赖的差异使得临床风险评估成为问题。在这项研究中，我们开发了基于系统选择的表观遗传学和临床参数的三级风险分层策略，以提高Barrett的食道监测效率。我们将高度不典型增生定义为进展的终点，Barrett‘s食道进展者患者定义为Barrett’s食管病患者，无不典型增生或低度不典型增生，后者后来发展为高度不典型增生或食管腺癌。我们分析了来自巴尔的摩退伍军人事务部、马里兰卫生保健系统和梅奥诊所的35例进展型和27例非进展型Barrett‘s食道患者的118例Barrett’s食道组织中的4个表观遗传学参数和3个临床参数。基于线性判别分析的2年和4年预测模型(受试者-操作者特征曲线下面积分别为0.8386和0.7910)，Barrett‘s食道标本被分层为高危(HR)、中危(IR)或低危(LR)组。这种3层分层方法既保留了2年模型的高特异度，又保留了4年模型的高敏感性。无进展生存率在3个风险组之间有显著差异，p = 为0.0022(HR与IR)和p<；0.0001(HR或IR与LR)。增量值分析表明，甲基化基因的数量对预测精度的影响最大。这种三层风险分层策略有可能对Barrett的食道监测的准确性和效率产生深远的影响。
Barrett's esophagus predisposes to esophageal adenocarcinoma. However, the value of endoscopic surveillance in Barrett's esophagus has been debated because of the low incidence of esophageal adenocarcinoma in Barrett's esophagus. Moreover, high inter-observer and sampling-dependent variation in the histologic staging of dysplasia make clinical risk assessment problematic. In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett's esophagus surveillance efficiency. We defined high-grade dysplasia as endpoint of progression, and Barrett's esophagus progressor patients as Barrett's esophagus patients with either no dysplasia or low-grade dysplasia who later developed high-grade dysplasia or esophageal adenocarcinoma. We analyzed 4 epigenetic and 3 clinical parameters in 118 Barrett's esophagus tissues obtained from 35 progressor and 27 non-progressor Barrett's esophagus patients from Baltimore Veterans Affairs Maryland Health Care Systems and Mayo Clinic. Based on 2-year and 4-year prediction models using linear discriminant analysis (area under the receiver-operator characteristic (ROC) curve: 0.8386 and 0.7910, respectively), Barrett's esophagus specimens were stratified into high-risk (HR), intermediate-risk (IR), or low-risk (LR) groups. This 3-tiered stratification method retained both the high specificity of the 2-year model and the high sensitivity of the 4-year model. Progression-free survivals differed significantly among the 3 risk groups, with p = 0.0022 (HR vs. IR) and p<0.0001 (HR or IR vs. LR). Incremental value analyses demonstrated that the number of methylated genes contributed most influentially to prediction accuracy. This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barrett's esophagus surveillance accuracy and efficiency.
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