Non-endoscopic screening biomarkers for Barrett’s oesophagus: from microarray analysis to the clinic
- P Lao-Sirieix1,
- A Boussioutas2,3,
- S R Kadri1,
- M O’Donovan1,4,
- I Debiram1,5,
- M Das1,
- L Harihar1,
- R C Fitzgerald1
- 1MRC-Cancer Cell Unit, Hutchison–MRC Research Centre, Cambridge, UK
- 2Department of Medicine, University of Melbourne, Western Hospital, Melbourne, Australia
- 3Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia
- 4Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK
- 5Experimental Cancer Medicine Centre, Department of Oncology, Addenbrooke’s Hospital, Cambridge, UK
- Correspondence to Dr R Fitzgerald, Hutchison–MRC Research Centre, Hills Road, Cambridge CB22 0XZ, UK; rcf{at}hutchison-mrc.cam.ac.uk
- Revised 9 July 2009
- Accepted 17 July 2009
- Published Online First 2 August 2009
Abstract
Background and aims: Barrett’s oesophagus 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 the disease a feasible option. However, due to the mixed cell population retrieved by the capsule sponge, biomarkers specific for Barrett’s oesophagus are required.
Methods: Three publically available microarray datasets were used to identify putative biomarkers present in Barrett’s oesophagus but absent from normal oesophagus and gastric mucosa. Validation was performed by qPCR (n = 10 each of normal oesophagus, Barrett’s oesophagus, gastric mucosa) and immunohistochemistry (normal oesophagus, n = 20; Barrett’s oesophagus, n = 21; gastric mucosa, n = 24; duodenum, n = 18). The biomarker was then prospectively evaluated on capsule sponge specimens from 47 patients with Barrett’s oesophagus 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 Barrett’s oesophagus compared to normal oesophagus (p<0.01) and gastric mucosa (p<0.01 and p<0.05, respectively). Immunohistochemistry confirmed that DDC protein expression was restricted to Barrett’s oesophagus but was confined to <1% of the cells within the crypt compartment. TFF3 protein was expressed to high levels at the luminal surface of Barrett’s oesophagus compared to absent expression in normal oesophagus and gastric mucosa (p<0.001). Using the capsule sponge 36/46 patients with Barrett’s oesophagus (one inadequate sample) and 6/96 controls were positive for TFF3 giving a sensitivity of 78% and a specificity of 94%.
Conclusions: TFF3 is a promising marker for Barrett’s oesophagus screening since it is expressed at the luminal surface of Barrett’s oesophagus but not in adjacent tissue types and may be applied to a non-endoscopic screening device.
Footnotes
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Funding This research was supported by the Medical Research Council, Cambridge Experimental Cancer Medicine Centre and the NIHR Cambridge Biomedical Research Centre.
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Competing interests None.
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Provenance and Peer review Not commissioned; externally peer reviewed.
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Ethics approval Ethics approval was obtained from the Cambridgeshire Research Ethics Committee on 17 October 2003.
