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Candidate serum metabolite biomarkers for differentiating gastroesophageal reflux disease, Barrett's esophagus, and high-grade dysplasia/esophageal adenocarcinoma.

ABSTRACT: Incidence of esophageal adenocarcinoma (EA), an often fatal cancer, has increased sharply over recent decades. Several important risk factors (reflux, obesity, smoking) have been identified for EA and its precursor, Barrett's esophagus (BE), but a key challenge remains identifying individuals at highest risk, since most with reflux do not develop BE, and most with BE do not progress to cancer. Metabolomics represents an emerging approach for identifying novel biomarkers associated with cancer development.We used targeted liquid chromatography-mass spectrometry (LC-MS) to profile 57 metabolites in 322 serum specimens derived from individuals with gastroesophageal reflux disease (GERD), BE, high-grade dysplasia (HGD), or EA, drawn from two well-annotated epidemiologic parent studies.Multiple metabolites differed significantly (P<0.05) between BE versus GERD (n=9), and between HGD/EA versus BE (n=4). Several top candidates (FDR q?0.15), including urate, homocysteine, and 3-nitrotyrosine, are linked to inflammatory processes, which may contribute to BE/EA pathogenesis. Multivariate modeling achieved moderate discrimination between HGD/EA and BE (AUC=0.75), with less pronounced separation for BE versus GERD (AUC=0.64).Serum metabolite differences can be detected between individuals with GERD versus BE, and between those with BE versus HGD/EA, and may help differentiate patients at different stages of progression to EA.

SUBMITTER: Buas MF

PROVIDER: S-EPMC5295138 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Candidate serum metabolite biomarkers for differentiating gastroesophageal reflux disease, Barrett's esophagus, and high-grade dysplasia/esophageal adenocarcinoma.

Buas Matthew F MF Gu Haiwei H Djukovic Danijel D Zhu Jiangjiang J Onstad Lynn L Reid Brian J BJ Raftery Daniel D Vaughan Thomas L TL

Metabolomics : Official journal of the Metabolomic Society 20170120 3

<h4>Introduction/objectives</h4>Incidence of esophageal adenocarcinoma (EA), an often fatal cancer, has increased sharply over recent decades. Several important risk factors (reflux, obesity, smoking) have been identified for EA and its precursor, Barrett's esophagus (BE), but a key challenge remains identifying individuals at highest risk, since most with reflux do not develop BE, and most with BE do not progress to cancer. Metabolomics represents an emerging approach for identifying novel biom ...[more]

PMID: 28190989

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Project description:Insulin and leptin have proliferative and anti-apoptotic effects. Ghrelin promotes gastric emptying and secretion of growth hormone and inhibits inflammation. We assessed whether diabetes mellitus and serum levels of insulin, leptin, and ghrelin are associated with gastroesophageal reflux disease (GERD) and Barrett's esophagus.We conducted a case-control study in 822 men undergoing colorectal cancer screening who were recruited to also undergo upper endoscopy. We identified 70 with Barrett's esophagus; 80 additional men with Barrett's esophagus were recruited shortly after their clinical diagnoses. Serum levels of insulin, leptin, and ghrelin were assayed in all 104 fasting men with Barrett's esophagus without diabetes and 271 without diabetes or Barrett's esophagus. Logistic regression was used to estimate the effects of diabetes and levels of insulin, leptin, and ghrelin on GERD and Barrett's esophagus.Among men with GERD, diabetes was inversely associated with Barrett's esophagus (adjusted odds ratio [OR] = 0.383; 95% confidence interval [CI]: 0.179-0.821). Among nondiabetics, hyperinsulinemia was positively associated with Barrett's esophagus, but the association was attenuated by adjustment for leptin and ghrelin. Leptin was positively associated with Barrett's esophagus, adjusting for obesity, GERD, and levels of insulin and ghrelin (OR for 3(rd) vs 1(st) tertile = 3.25; 95% CI: 1.29-8.17); this association was stronger in men with GERD (P = .01 for OR heterogeneity). Ghrelin was positively associated with Barrett's esophagus (OR for an increment of 400 pg/mL = 1.39; 95% CI: 1.09-1.76), but inversely associated with GERD (OR for 3(rd) vs 1(st) tertile = 0.364; 95% CI: 0.195-0.680).Based on a case-control study, leptin was associated with Barrett's esophagus, particularly in men with GERD. Serum insulin level was associated with Barrett's esophagus, but might be mediated by leptin. Serum ghrelin was inversely associated with GERD, as hypothesized, but positively associated with Barrett's esophagus, contrary to our hypothesis. Additional studies are needed in men and women to replicate these findings.

Dataset Information

Candidate serum metabolite biomarkers for differentiating gastroesophageal reflux disease, Barrett's esophagus, and high-grade dysplasia/esophageal adenocarcinoma.

Publications

Candidate serum metabolite biomarkers for differentiating gastroesophageal reflux disease, Barrett's esophagus, and high-grade dysplasia/esophageal adenocarcinoma.

Similar Datasets

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