Elucidating the role of fatty acid reprogramming in ovarian cancer: Insights cross-talk between blood, subcutaneous fat, and ovarian cancer tissues

Xiaocui Zhong¹Mamona Bilal¹Yanqiu Zhou¹Xiaojia Yang²Zuchao Qin¹Qibing Li¹Yang Yang²Ting-Li Han^1*Min Li^1*

• ¹Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
• ²Chongqing Medical University, Chongqing, China

Aberrant fatty acid (FA) metabolism is increasingly recognized as a significant factor in ovarian cancer (OC) progression, although the comprehensive metabolic alterations across different body tissues remain unclear. In this study, sixteen OC patients and twenty-nine non-cancer (NC) patients were recruited for metabolic profiling using a global and targeted metabolomic strategy based on a gas chromatography-hydrogen flame ionization detector (GC-FID). The patient survival was followed up to 3 years, and PFS was calculated. Our findings revealed distinct metabolite profiles that differentiate OC from NC groups across all sample types. We found seven, nine, and thirteen significant metabolites in subcutaneous fat, plasma, and ovarian tissue respectively. In particular, docosahexaenoic acid (DHA) and arachidonic acid (AA) levels were notably elevated in all sample types of OC patients. Furthermore, receiver operating characteristic (ROC) analysis highlight that three plasma FA showed the best specificity and sensitivity in differentiating the OC group from the NC group (Area Under The Curve, AUC > 0.89), including caprylic acid, myristoleic acid, and tetracosaenoic acid. Most of the significant FA in subcutaneous fat and ovarian tissue showed a high risk of OC. However, caprylic acid and tetracosanoic acid were identified as protective factors in the plasma sample. We also found that high levels of linoelaidic acid in subcutaneous fat and palmitelaidic acid in ovarian tissue were associated with poor prognosis. Pathway analysis suggested that these fatty acids may influence OC progression through the FA synthesis and regulation of the inflammatory mediator and ferroptosis. Overall, this study elucidates the reprogramming of FA metabolism across several biospecimens in OC patients, providing the mechanisms driving OC progression and highlighting potential biomarkers and targeted therapeutic interventions.