Abstract
OBJECTIVE: To analyze the lipidomic profile of ESCC patients, link changes in cancer lipid metabolism to gene expression changes, and provide new insights into the diagnosis and treatment of ESCC patients in the Kazakh Xinjiang ethnic group. METHODS: By integrating the lipidome and transcriptome results, genes related to differential lipid metabolites in Kazakh ESCC patients were identified, and the effects of the key gene AMPK on lipid metabolism in ESCC cells were investigated by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC‒MS/MS). RESULT: Through absolute lipid quantification analysis of two serum samples, 13 classes of lipids were detected, with triglycerides (TAGs) being the most abundant. Phosphatidylcholine (LPC), phosphatidylethanolamine (PE), and ceramide (Cer) were the lipid categories with significant differences between the two groups. Transcriptome analysis revealed that genes related to fatty acid synthesis, carnitine biosynthesis, and other lipid metabolism pathways were enriched in the tumor tissue. Integrative analysis of the two groups suggested that fatty acid synthesis, fatty acid metabolism, lipid degradation, cholesterol metabolism, and the AMPK signaling pathway were enriched in tumor tissue. UPLC‒MS/MS was used to perform targeted lipidomic analysis of AMPK-knockdown esophageal squamous cell carcinoma cells, suggesting that AMPK may be involved in the reprogramming of lipid metabolism in Kazakh ESCC patients. CONCLUSIONS: Lipid metabolic reprogramming occurs in the tumor tissue of Kazakh ESCC patients, and there is a correlation between AMPK activity and lipid metabolism, which suggests a potential therapeutic target for the treatment of Kazakh ESCC.