Signatures of field cancerization: a step towards earlier detection of esophageal adenocarcinoma

In the March 2017 issue of Neoplasia Reed et al. report on a metabolic signature in the normal esophageal squamous tissue in patients with esophageal adenocarcinoma (EAC) arising in a background of Barrett’s esophagus (BE). The study utilized ¹H-nuclear magnetic resonance (¹H-NMR) to assess complex metabolic mixtures within tissue samples from normal squamous, BE- and EAC-affected areas of the esophagus to identify individual metabolites and metabolic signatures associated with each state. A metabolic signature was identified that distinguished normal squamous epithelium from BE patients with EAC (n=30) from normal squamous epithelium from patients with dyspeptic symptoms but no detectable BE or EAC (n=68). The signature produced by a partial least squares discriminant analysis (PLS-DA) model included the metabolites 3-hydroxybutyrate, succinate, formate, acetate, glycerophosphocholine, ADP and lactate. The authors discussed potential rationale for the observed differences in these metabolites in the squamous epithelium of patients with EAC, including the possibility that the elevated levels of formate may be related to ATP and NAD(P)H synthesis as cells adapt to changes in energy requirements in the cancer-bearing state. Additional studies will be required to understand why these particular metabolites are altered in the normal squamous mucosa adjacent to EAC.