Endometrial Cancer Is Associated with Altered Metabolism and Composition of Fatty Acids

Abstract

Endometrial cancer (EC) is a complex gynecologic malignancy that requires a deeper understanding of its molecular basis to improve therapeutic strategies. In this study, we investigated the role of fatty acid (FA) reprogramming in the progression of EC. We analyzed FA profiles to identify the stage-specific changes and gene expression profiles of key enzymes involved in FA synthesis, desaturation, elongation, transport, and oxidation at different stages of EC. Our results show that EC tissues have lower levels of saturated FA and branched-chain FA, higher levels of very long-chain FA, n-3 polyunsaturated FA (PUFA), and monounsaturated FA, with the exception of myristoleic acid. The differences in n-6 PUFA were inconsistent. Gene expression analysis revealed the upregulation of key enzymes controlling de novo FA synthesis, including ACACA, FASN, SCD1, and ELOVL1. In contrast, the expression of genes related to FA transport in the cell and β-oxidation was downregulated. The expression of some genes related to PUFA metabolism was upregulated, while others were downregulated. These results demonstrate a reprogramming of lipid metabolism in EC tissues and suggest potential targets for novel therapeutic interventions in EC.