Elsevier

Neoplasia

Volume 19, Issue 3, March 2017, Pages 165-174
Neoplasia

Metabolomic Evidence for a Field Effect in Histologically Normal and Metaplastic Tissues in Patients with Esophageal Adenocarcinoma1

https://doi.org/10.1016/j.neo.2016.11.003Get rights and content
Under a Creative Commons license
open access

Abstract

Patients with Barrett's esophagus (BO) are at increased risk of developing esophageal adenocarcinoma (EAC). Most Barrett's patients, however, do not develop EAC, and there is a need for markers that can identify those most at risk. This study aimed to see if a metabolic signature associated with the development of EAC existed. For this, tissue extracts from patients with EAC, BO, and normal esophagus were analyzed using 1H nuclear magnetic resonance. Where possible, adjacent histologically normal tissues were sampled in those with EAC and BO. The study included 46 patients with EAC, 7 patients with BO, and 68 controls who underwent endoscopy for dyspeptic symptoms with normal appearances. Within the cancer cohort, 9 patients had nonneoplastic Barrett's adjacent to the cancer suitable for biopsy. It was possible to distinguish between histologically normal, BO, and EAC tissue in EAC patients [area under the receiver operator curve (AUROC) 1.00, 0.86, and 0.91] and between histologically benign BO in the presence and absence of EAC (AUROC 0.79). In both these cases, sample numbers limited the power of the models. Comparison of histologically normal tissue proximal to EAC versus that from controls (AUROC 1.00) suggests a strong field effect which may develop prior to overt EAC and hence be useful for identifying patients at high risk of developing EAC. Excellent sensitivity and specificity were found for this model to distinguish histologically normal squamous esophageal mucosa in EAC patients and healthy controls, with 8 metabolites being very significantly altered. This may have potential diagnostic value if a molecular signature can detect tissue from which neoplasms subsequently arise.

Abbreviations

EAC
esophageal adenocarcinoma
BO
Barrett's esophagus
HGD
high-grade dysplasia
NMR
nuclear magnetic resonance
PCA
principle component analysis
PLS-DA
partial least squares discriminant analysis
ML-PLS-DA
multilevel partial least squares discriminant analysis
AUROC
area under the receiver operator curve

Cited by (0)

1

Funding: This work was supported by a grant by the The Bupa Foundation to R. S. M. R. was in part supported by the COSMOS EU grant (FP7-INFRASTRUCTURES-2012-1-312941) under which all data were deposited to MetaboLights.

2

Equal first authors.