Serum metabolomic profiling for patients with adenocarcinoma of the esophagogastric junction.

introductionThe incidence of adenocarcinoma in the esophagogastric junction (AEG) has increased in the recent years. AEG is reported to have a worse prognosis compared with tumor confined to the stomach (non-AEG). Although the metabolic changes of non-AEG have been investigated in extensive studies, little effort focused on the metabolic profiling of AEG serum.

objectivesHere we report an untargeted gas chromatography-mass spectrometry (GC-MS) method to explore the abnormal metabolism underlying AEG.

methodsGC-MS-based untargeted metabolomics approach combined with multivariate statistical analyses were used to study the metabolic profiling of serum samples from AEG patients (n = 70), non-AEG patients (n = 70) and health controls (n = 71).

resultsA novel serum metabolic profiling of 18 metabolites from patients of AEG and non-AEG was indicated, in comparison with health controls. Moreover, AEG and non-AEG were also well-classified with 9 distinguishing metabolites including hypoxanthine, alanine, proline, pyroglutamate, glycine, lactate, succinic acid, glutamate and kynurenine, which produced a discriminatory model with an area under the Receiver Operating Characteristic (ROC) curve of 0.852, suggesting a distinct metabolic signature of AEG. Importantly, lactate and glutamate disclosed outcome-prediction values by multivariate cox-proportional hazard model and Kaplan-Meier method based on follow-up information for 2-5 years.

conclusionThis is the first metabolomics study to identify serum metabolic signature of AEG. The distinguishing metabolites show a promising application on clinical diagnose and outcome prediction, and allow us to unveil several key metabolic variations coexisting in AEG, which may aid to understand the underlying metabolic mechanisms.