Serum Metabolomic Signatures of Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma

Lymph node metastasis was recently proven to be the single most important prognostic factor for esophageal cancer, an important malignant tumor with poor prognosis. A global metabolomics approach was applied to study lymph node metastasis of esophageal squamous cell carcinoma (ESCC). Metabolomics analyses were performed using gas chromatography/mass spectrometry together with univariate and multivariate statistical analyses. There were clear metabolic distinctions between ESCC patients and healthy subjects. ESCC patients could be well-classified according to lymph node metastasis. We further identified a series of differential serum metabolites for ESCC and lymph node metastatic ESCC patients, suggesting metabolic dysfunction in proliferation (aerobic glycolysis, glutaminolysis, fatty acid metabolism, and branched-chain amino acid consumption), apoptosis, migration, immune escape, and oxidative stress of cancer cells in metastatic ESCC patients. In total, three serum metabolites (valine, gamma-aminobutyric acid, and pyrrole-2-carboxylic acid) were selected by binary logistic regression analysis, and their combined use resulted in high diagnostic capacity for ESCC metastasis by receiver operating characteristic analysis. The present metabolomics study staged ESCC patients by lymph node metastasis, and the results suggest promising applications of this approach in prognostic prediction, tailored therapeutics, and understanding the pathological mechanisms of poor prognosis of ESCC patients.