Complex metabolic interactions between ovary, plasma, urine, and hair in ovarian cancer

Abstract

Ovarian cancer (OC) is the third most common malignant tumor of women accompanied by alteration of systemic metabolism, yet the underlying interactions between the local OC tissue and other system biofluids remain unclear. In this study, we recruited 17 OC patients, 16 benign ovarian tumor (BOT) patients, and 14 control patients to collect biological samples including ovary plasma, urine, and hair from the same patient. The metabolic features of samples were characterized using a global and targeted metabolic profiling strategy based on Gas chromatography-mass spectrometry (GC-MS). Principal component analysis (PCA) revealed that the metabolites display obvious differences in ovary tissue, plasma, and urine between OC and non-malignant groups but not in hair samples. The metabolic alterations in OC tissue included elevated glycolysis (lactic acid) and TCA cycle intermediates (malic acid, fumaric acid) were related to energy metabolism. Furthermore, the increased levels of glutathione and polyunsaturated fatty acids (linoleic acid) together with decreased levels of saturated fatty acid (palmitic acid) were observed, which might be associated with the anti-oxidative stress capability of cancer. Furthermore, how metabolite profile changes across differential biospecimens were compared in OC patients. Plasma and urine showed a lower concentration of amino acids (alanine, aspartic acid, glutamic acid, proline, leucine, and cysteine) than the malignant ovary. Plasma exhibited the highest concentrations of fatty acids (stearic acid, EPA, and arachidonic acid), while TCA cycle intermediates (succinic acid, citric acid, and malic acid) were most concentrated in the urine. In addition, five plasma metabolites and three urine metabolites showed the best specificity and sensitivity in differentiating the OC group from the control or BOT groups (AUC > 0.90) using machine learning modeling. Overall, this study provided further insight into different specimen metabolic characteristics between OC and non-malignant disease and identified the metabolic fluctuation across ovary and biofluids.