Fatty Acid Metabolism Regulators Have Pivotal Roles in the Pathogenesis of Ovarian Carcinoma

This study elucidates how dysregulated fatty acid (FA) metabolism regulators—including FABP4, FABP5, PPARα, and PPARγ—contribute to the biological and biomechanical characteristics of epithelial ovarian carcinoma (EOC). Human ovarian surface epithelium (HOSE) cells and two EOC lines (AMOC-2, serous adenocarcinoma; ES2, clear cell carcinoma) were cultured in 3D spheroid systems to compare morphology, gene expression, and metabolic profiles. Cancer-derived spheroids displayed weak cohesion and non-spherical morphologies, correlating with reduced expression of tight-junction proteins (ZO-1, claudin-1). Multiomic and Seahorse metabolic analyses revealed that FABP4 and FABP5 were upregulated in ES2 cells, while PPARγ was elevated in AMOC-2, leading to divergent metabolic phenotypes. Kaplan–Meier analysis of patient cohorts further confirmed that high expression of these regulators predicted poorer prognosis in serous ovarian carcinoma. The findings identify FA metabolic regulators as drivers of tumor spheroid fragility, altered energy metabolism, and potential therapeutic targets in ovarian cancer.