TY - JOUR
T1 - Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features
AU - Sato, Fumiaki
AU - Jin, Zhe
AU - Schulmann, Karsten
AU - Wang, Jean
AU - Greenwald, Bruce D.
AU - Ito, Tetsuo
AU - Kan, Takatsugu
AU - Hamilton, James P.
AU - Yang, Jian
AU - Paun, Bogdan
AU - David, Stefan
AU - Olaru, Alexandru
AU - Cheng, Yulan
AU - Mori, Yuriko
AU - Abraham, John M.
AU - Yfantis, Harris G.
AU - Wu, Tsung Teh
AU - Fredericksen, Mary B.
AU - Wang, Kenneth K.
AU - Canto, Marcia
AU - Romero, Yvonne
AU - Feng, Ziding
AU - Meltzer, Stephen J.
PY - 2008/4/2
Y1 - 2008/4/2
N2 - Background: 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. Methods and Findings: 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 Barretts 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 0.79110, 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 he 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. Conclusions: This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barrett's esophagus surveillance accuracy and efficiency.
AB - Background: 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. Methods and Findings: 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 Barretts 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 0.79110, 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 he 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. Conclusions: This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barrett's esophagus surveillance accuracy and efficiency.
UR - http://www.scopus.com/inward/record.url?scp=44849142186&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0001890
DO - 10.1371/journal.pone.0001890
M3 - Article
C2 - 18382671
AN - SCOPUS:44849142186
SN - 1932-6203
VL - 3
JO - PloS one
JF - PloS one
IS - 4
M1 - e1890
ER -