TY - JOUR
T1 - Methylation biomarker panel performance in esophacap cytology samples for diagnosing Barrett's esophagus
T2 - A prospective validation study
AU - Wang, Zhixiong
AU - Kambhampati, Swetha
AU - Cheng, Yulan
AU - Ma, Ke
AU - Simsek, Cem
AU - Tieu, Alan H.
AU - Abraham, John M.
AU - Liu, Xi
AU - Prasath, Vishnu
AU - Duncan, Mark
AU - Stark, Alejandro
AU - Trick, Alexander
AU - Tsai, Hua Ling
AU - Wang, Hao
AU - He, Yulong
AU - Khashab, Mouen A.
AU - Ngamruengphong, Saowanee
AU - Shin, Eun J.
AU - Wang, Tza Huei
AU - Meltzer, Stephen J.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Purpose: Barrett's esophagus is the only known precursor of esophageal adenocarcinoma (EAC). Although endoscopy and biopsy are standard methods for Barrett's esophagus diagnosis, their high cost and risk limit their use as a screening modality. Here, we sought to develop a Barrett's esophagus detection method based on methylation status in cytology samples captured by EsophaCap using a streamlined sensitive technique, methylation on beads (MOB). Experimental Design: We conducted a prospective cohort study on 80 patients (52 in the training set; 28 in the test set). We used MOB to extract and bisulfite-convert DNA, followed by quantitative methylation-specific PCR to assess methylation levels of 8 previously selected candidate markers. Lasso regression was applied to establish a prediction model in the training set, which was then tested on the independent test set. Results: In the training set, five of eight candidate methylation biomarkers (p16, HPP1, NELL1, TAC1, and AKAP12) were significantly higher in Barrett's esophagus patients than in controls. We built a four-biomarker-plus-age lasso regression model for Barrett's esophagus diagnosis. The AUC was 0.894, with sensitivity 94.4% [95% confidence interval (CI), 71%–99%] and specificity 62.2% (95% CI, 44.6%–77.3%) in the training set. This model also performed with high accuracy for Barrett's esophagus diagnosis in an independent test set: AUC ¼ 0.929 (P < 0.001; 95% CI, 0.810%–1%), with sensitivity¼78.6% (95% CI, 48.8%–94.3%) and specificity ¼ 92.8% (95% CI, 64.1%–99.6%). Conclusions: EsophaCap, in combination with an epigenetic biomarker panel and the MOB method, is a promising, well-tolerated, low-cost esophageal sampling strategy for Barrett's esophagus diagnosis. This approach merits further prospective studies in larger populations.
AB - Purpose: Barrett's esophagus is the only known precursor of esophageal adenocarcinoma (EAC). Although endoscopy and biopsy are standard methods for Barrett's esophagus diagnosis, their high cost and risk limit their use as a screening modality. Here, we sought to develop a Barrett's esophagus detection method based on methylation status in cytology samples captured by EsophaCap using a streamlined sensitive technique, methylation on beads (MOB). Experimental Design: We conducted a prospective cohort study on 80 patients (52 in the training set; 28 in the test set). We used MOB to extract and bisulfite-convert DNA, followed by quantitative methylation-specific PCR to assess methylation levels of 8 previously selected candidate markers. Lasso regression was applied to establish a prediction model in the training set, which was then tested on the independent test set. Results: In the training set, five of eight candidate methylation biomarkers (p16, HPP1, NELL1, TAC1, and AKAP12) were significantly higher in Barrett's esophagus patients than in controls. We built a four-biomarker-plus-age lasso regression model for Barrett's esophagus diagnosis. The AUC was 0.894, with sensitivity 94.4% [95% confidence interval (CI), 71%–99%] and specificity 62.2% (95% CI, 44.6%–77.3%) in the training set. This model also performed with high accuracy for Barrett's esophagus diagnosis in an independent test set: AUC ¼ 0.929 (P < 0.001; 95% CI, 0.810%–1%), with sensitivity¼78.6% (95% CI, 48.8%–94.3%) and specificity ¼ 92.8% (95% CI, 64.1%–99.6%). Conclusions: EsophaCap, in combination with an epigenetic biomarker panel and the MOB method, is a promising, well-tolerated, low-cost esophageal sampling strategy for Barrett's esophagus diagnosis. This approach merits further prospective studies in larger populations.
UR - http://www.scopus.com/inward/record.url?scp=85064160995&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064160995&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-18-3696
DO - 10.1158/1078-0432.CCR-18-3696
M3 - Article
C2 - 30670490
AN - SCOPUS:85064160995
SN - 1078-0432
VL - 25
SP - 2127
EP - 2135
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -