Increased PXR and suppressed T-cell signaling are associated with malignant degeneration of Barrett's esophagus

Barrett's esophagus (BE) is the precursor lesion for esophageal adenocarcinoma (EAC). To detect EAC in early stage, patients with BE undergo endoscopic surveillance. Surveillance cohorts largely consist of non-dysplastic Barrett's esophagus (NDBE) patients with a low annual progression risk (<0.5%). Predictive biomarkers for malignant progression of NDBE could improve efficacy of surveillance. Biomarker research has mostly focused on aberrant protein expression on BE epithelial cells. Moreover, insight in cell signaling driving malignant transformation is unknown. This study uses a data-driven approach to analyze tumor-stroma interaction in NDBE which progressed to high grade dysplasia (HGD) or EAC. Overall design: In this case control study, we performed RNA sequencing analysis on index NDBE biopsies from six patients who during long term follow-up progressed and seven who not progressed to HGD/EAC. For control samples, squamous and duodenum tissues from BE patients were analysed. For validation we used qPCR.