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Non-endoscopic screening biomarkers for Barrett’s oesophagus: From microarray analysis to the clinic
  1. Pierre Lao-Sirieix (pss29{at}cam.ac.uk)
  1. MRC-Hutchison Research Centre, Cambridge, United Kingdom
    1. Alex Boussioutas (alexb{at}unimelb.edu.au)
    1. Peter MacCallum Cancer Centre, East Melbourne, Australia
      1. Sudarshan R Kadri (sk543{at}cam.ac.uk)
      1. MRC-Hutchison Research Centre, Cambridge, United Kingdom
        1. Maria O'Donovan (mo259{at}cam.ac.uk)
        1. MRC-Hutchison Research Centre, Cambridge, United Kingdom
          1. Irene Debiram (id213{at}medschl.cam.ac.uk)
          1. MRC-Hutchison Research Centre, Cambridge, United Kingdom
            1. madhumita Das (md446{at}cam.ac.uk)
            1. MRC-Hutchison Research Centre, Cambridge, United Kingdom
              1. Lakshmi Harihar (lh316{at}hermes.cam.ac.uk)
              1. MRC-Hutchison Research Centre, Cambridge, United Kingdom
                1. Rebecca C Fitzgerald (rcf{at}hutchison-mrc.cam.ac.uk)
                1. MRC-Hutchison Research Centre, Cambridge, United Kingdom

                  Abstract

                  Background & aims: Barrett’s oesophagus (BE) predisposes to oesophageal adenocarcinoma but the majority of patients are undiagnosed. A novel non-endoscopic cytological screening device, called a capsule sponge, makes population-based screening for BE a feasible option. However, due to the mixed cell population retrieved by the capsule sponge, biomarkers specific for BE are required.

                  Methods: Three publically available microarray datasets were used to identify putative biomarkers present in BE but absent from squamous oesophagus (NE) and gastric mucosa (GM). Validation was performed by QPCR (n=10 each of NE, BE, GM) and immunohistochemistry (NE n=20, BE n=21, GM n=24, duodenum n=18). The biomarker was then prospectively evaluated on capsule sponge specimens from 29 BE patients and 99 healthy controls.

                  Results: 2/14 genes identified, dopa-decarboxylase (DDC) and Trefoil Factor 3 (TFF3), were confirmed by QPCR to be upregulated in BE compared to NE (p<0.01) and GM (p<0.01 and p<0.05 respectively). Immunohistochemistry confirmed that DDC protein expression was restricted to BE but was confined to <1% of the cells within the crypt compartment. TFF3 protein was expressed to high levels at the luminal surface of BE compared to absent expression in NE and GM (p<0.001). Using the capsule sponge 20/29 BE patients and 6/96 controls were positive for TFF3 giving a positive predictive value of 77% and a negative predictive value of 91%.

                  Conclusions: TFF3 is a promising marker for BE screening since it is expressed at the luminal surface of BE but not in adjacent tissue types and may be applied to a non-endoscopic screening device.

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