Abstract

e12571 Background: Chemotherapy-induced cognitive impairment, also known as 'chemobrain', is widely recognized as a frequent adverse effect of chemotherapy, occurs in 10-40% of all cancer patients. Those cancer survivors suffer from poor concentration, memory, abstract reasoning, and motor dysfunction. The etiology is unclear. In our study, we analyzed the metabolite panels in breast cancer patients with vs. without chemotherapy trying to identify metabolic mediators of neurologic injury. Methods: We obtained plasma sample from 18 breast cancer patients, 9 received chemotherapy prior to blood drawn; while the other 9 had no systemic therapy. The plasma samples were sent for mass spectroscopy. Each metabolites level was normalized, and the two groups were compared in each metabolite by t-test with statistical significance corrected for multiple comparisons using the Holm-Sidak method. Results: We identified 57 amines and their metabolites; 106 carbohydrate related metabolites, and 228 lipid molecules. While amino acid, and carbohydrate did not show significant difference, phosphatidylcholine level in the chemotherapy treated group demonstrated lower level in the patients received chemotherapy. Among 59 phosphatidylcholine identified, 6 variants were significantly lower in the chemo group compare with non chemo group. Additionally the sum of all phosphatidylcholine variants was diminished in the chemotherapy treated patients compared with untreated controls. No other differences in plasma lipid levels were identified. Conclusions: Phosphatidylcholine is a major component of cell membranes and lipid rafts which are critical elements in nerve conduction. It also plays a role as the precursor to the neurotransmitter acetylcholine. The finding that phosphatidylcholine is significantly different between chemotherapy treated vs. the no chemotherapy group raises the possibility that lipid metabolism contributes to chemotherapy-induced cognitive impairment and further experiments are planned to explore this hypothesis.

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