Background: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent types of upper gastrointestinal malignancies. This work aimed to identify potential biomarkers for early screening for ESCC and characterize the systemic metabolic disturbances underlying ESCC using multi-platform metabolomics analysis.
Methods: We divided 239 patients (the early-stage ESCC patients, n = 132; Healthy controls, n = 107) into discovery and validation sets after matching age and sex. Integrated statistical and multi-platform serum metabolomics analyses were used to screen and validate significant metabolites linked to ESCC patients.
Results: Multi-platform metabolomics analyses showed that amino acid and lipid metabolism were crucial in the etiology of ESCC. Five metabolites, tryptophan (Trp), citrulline, l-carnitine, lysine, and acetyl-carnitine, were selected as potential biomarkers to establish a diagnosis panel, which showed high accuracy in distinguishing ESCC patients from healthy controls (area under the receiver operating characteristic curve, 0.873, 95% confidence interval [CI]: 0.825-0.925).
Conclusions: This work laid the groundwork for understanding the etiology of ESCC. The diagnostic panel showed potential usefulness in early-stage ESCC diagnosis in clinical practice.
Keywords: Diagnostic biomarkers; Esophageal squamous cell carcinoma; Metabolic network; Targeted metabolomics; Untargeted metabolomics.
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