Skip to content

Medicine Matters

Sharing successes, challenges and daily happenings in the Department of Medicine

Medicine Matters Home Article of the Week Methylation Biomarker Panel Performance in EsophaCap Cytology Samples for Diagnosing Barrett’s Esophagus: A Prospective Validation Study

Methylation Biomarker Panel Performance in EsophaCap Cytology Samples for Diagnosing Barrett’s Esophagus: A Prospective Validation Study

ARTICLE: Methylation Biomarker Panel Performance in EsophaCap Cytology Samples for Diagnosing Barrett's Esophagus: A Prospective Validation Study

AUTHORS: Zhixiong Wang, Swetha Kambhampati, Yulan Cheng, Ke MaCem Simsek, Alan H Tieu, John M Abraham, Xi Liu, Vishnu Prasath, Mark D Duncan, Alejandro Stark, Alexander Trick, Hua-Ling Tsai, Hao Wang, Yulong He, Mouen A Khashab, Saowanee Ngamruengphong, Eun J Shin, Tza-Huei Wang and Stephen J. Meltzer

JOURNAL: Clin Cancer Res. 2019 Jan 22. pii: clincanres.3696.2018. doi: 10.1158/1078-0432.CCR-18-3696. [Epub ahead of print]

Abstract

PURPOSE: Barrett's esophagus (BE) is the only known precursor of esophageal adenocarcinoma (EAC). Although endoscopy and biopsy are standard methods for BE diagnosis, their high cost and risk limit their use as a screening modality. Here, we sought to develop a BE 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 employed MOB to extract and bisulfite-convert DNA, followed by qMSP 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, 5 of 8 candidate methylation biomarkers (p16, HPP1, NELL1, TAC1, and AKAP12) were significantly higher in BE patients than in controls. We built a 4-biomarker-plus-age lasso regression model for BE diagnosis. The AUC was 0.894, with sensitivity 94.4% (95% 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 BE diagnosis in an independent test set: AUC= 0.929 (P<0.001, 95% CI 0.810~1), with sensitivity = 78.6% (95% CI 48.8%~94.3%) and specificity = 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 BE diagnosis. This approach merits further prospective studies in larger populations.

For a link to the full article, click here: http://clincancerres.aacrjournals.org/content/early/2019/01/22/1078-0432.CCR-18-3696.long

Link to abstract online: https://www.ncbi.nlm.nih.gov/pubmed/?term=Methylation+Biomarker+Panel+Performance+in+EsophaCap+Cytology+Samples+for+Diagnosing+Barrett%27s+Esophagus%3A+A+Prospective+Validation+Study

nv-author-image

Kelsey Bennett