Abstract
Thyroid cancer (TC) is the most common endocrine cancer with a sharply increasing incidence worldwide in recent years. Multiple factors including genetics, radiation, iodine, autoimmune disease, and exposure to environmental endocrine–disrupting chemicals (EDCs) may be related to the incidence of TC. Polybrominated diphenyl ethers (PBDEs) have been extensively used in electronic production, soft furnishings, fabrics, and paints as flame retardants since the 1980s. As a typical EDCs, high PBDEs exposure is associated with an increased risk of TC. However, interference with the metabolic signature in PBDEs exposure–related TC has not been studied. In this study, eight congeners of PBDEs were determined in serum from 111 patents with papillary thyroid cancer (PTC) and 111 healthy participants based on case–control epidemiology using gas chromatography–atmospheric pressure chemical ionization–tandem mass spectrometry (GC-APCI-MS/MS). Based on the tertile distribution of total PBDEs concentrations in 59 participants, metabolomics analysis was performed by ultra-high performance liquid chromatography coupled to hybrid quadrupole-Orbitrap MS. The 29 identified metabolites were correlated with PBDEs exposure (Partial correlation analysis, P < 0.05). Furthermore, (+/-)-octopamine and 5-hydroxyindole, which modify the actions of neurotransmitters, were identified as potentially disturbed metabolite markers of TC upon PBDEs exposure. The PBDEs disturbed the glycerophospholipids, sphingolipids, and taurine and hypotaurine metabolism, which showed that neurotransmitters, oxidative stress, and inflammation were the sensitive pathways in PTC. These are the first findings on metabolic disturbance in PTC associated with PBDEs exposure by MS nontargeted metabolomics.