Abstract

Introduction: Purpose: To evaluate MUC-2 and CDX-2 expression as biomarkers for Barrett's Esophagus (BE) using esophageal brushing and quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). Background: Esophageal adenocarcinoma (EAC) starts as BE which is a direct consequence of gastroesophageal reflux (GERD). EAC usually presents with advanced disease in the United States and carries a poor prognosis. More than half of EAC patients report minimal or no GERD symptoms prior to presenting with EAC. If dysplastic BE or early EAC are detected, treatments can cure the disease. Sensitive and specific biomarkers for BE are needed to noninvasively detect dysplastic BE and early EAC in this population. Mucin 2(MUC-2) is secreted by intestinal goblet cells and CDX-2 is a caudal-type homeobox protein specific for intestinal epithelial cells. Both proteins are associated with esophageal intestinal metaplasia (BE). Methods: 40 patients had upper endoscopy (EGD) performed with esophageal brushing, 37 men and 7 women with a mean age of 62.5 years. Brushed samples were assayed for messenger RNA (mRNA) expression of MUC-2 and CDX-2 by RT-qPCR. A house keeping gene, beta-actin served as the reference gene. Delta delta cycle threshold (delta delta Ct) values were compared to histology read by a single expert GI pathologist blinded to the RT-qPCR data (gold standard). All patients had a prior diagnosis of BE or high-risk for BE. Histology demonstrated 17 patients with BE and 23 without. Delta delta Ct values were compared between the two groups. A lower delta delta Ct correlates with higher mRNA expression. Results: Delta delta Ct values for MUC-2 and CDX-2 expression were significantly lower for BE patients compared to those patients without BE (P value<0.001). The Receiver Operating Curve (ROC) for MUC-2 and CDX-2 measurements showed an area under the curve (AUC; % test accuracy) of 0.982 (98.2%) and 0.881 (88.1%),respectively. Conclusion: mRNA expression of MUC-2 and CDX-2 by RT-qPCR are promising biomarkers with high accuracy for identifying BE. Future studies are needed to evaluate these biomarkers using noninvasive cell retrieval methods (Cytosponge and balloon capsule).

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