| Sumario: | Various studies have demonstrated metabolic disorders in patients with esophageal squamous cell carcinoma (ESCC), although their potential role in ESCC development remains unclear. Here, we investigated alterations in the serum and fecal metabolomes of 23 ESCC patients and 23 healthy controls using untargeted metabolomics. Further analysis identified lauric acid as a biomarker for ESCC through targeted metabolomics, with validation in 88 ESCC patients and 44 healthy controls. Then, we examined the effects and mechanisms of lauric acid on EC109 cell physiological functions. Significant alterations occurred in serum and fecal samples from ESCC patients versus healthy controls, with lipid metabolites and associated pathways showing the most pronounced changes. Lauric acid was identified as a characteristic altered metabolite and an independent risk factor for ESCC (OR = 1.71, 95% CI: 1.05–2.79, p < 0.05). Mechanistic studies demonstrated that lauric acid promotes EC109 survival, invasion, and migration by interacting with the highly expressed fatty acid receptor GPR84 in ESCC tissues. Our research provides new insights into the relationship between lipid metabolism disorders and ESCC development, suggesting that lauric acid serves as an ESCC risk factor and may offer therapeutic intervention avenues.
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