作为最常见的内分泌癌症,在过去的三十年中,甲状腺癌(TC)在全球范围内急剧增加。TC发病率的增长可能是通过遗传学计算的,辐射,碘,自身免疫性疾病,和暴露于环境内分泌干扰化学物质(EDCs)。多溴联苯醚(PBDEs),作为典型的EDCs,已广泛用于塑料,电子,家具,自20世纪80年代以来,纺织品作为阻燃剂,研究表明,他们的暴露与TC风险之间存在显著相关性。即便如此,多溴二苯醚暴露对TC代谢特征的影响仍有待探索。在这项研究中,根据病例对照流行病学,采用气相色谱-常压化学电离-串联质谱(GC-APCI-MS/MS),从111名甲状腺乳头状癌(PTC)患者和111名健康参与者的血清中测定了8种多溴二苯醚同源物.根据59名参与者的多溴二苯醚总浓度的三元分布,代谢组学分析进一步通过超高效液相色谱与杂合四极杆-OrbitrapMS偶联进行。在偏相关分析中,29种代谢产物与多溴二苯醚暴露相关(P<0.05)。此外,多溴二苯醚破坏了甘油磷脂的代谢,鞘脂,牛磺酸,和低牛磺酸,表明神经递质,氧化应激,炎症是PTC中受影响的脆弱途径。此外,(±)-章鱼胺和5-羟基吲哚,两者都调节神经递质的作用,暴露于多溴二苯醚后,作为TC的潜在干扰代谢物标志物出现。本研究分析了多溴二苯醚对PTC代谢变化的影响,并进一步探讨了可能的生物标志物,这有助于我们深入了解PBDEs对TC影响的可能机制。
As the most common endocrine cancer, thyroid cancer (TC) has sharply increased globally over the past three decades. The growing incidence of TC might be counted by genetics, radiation, iodine, autoimmune disease, and exposure to environmental endocrine-disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs), being typical EDCs, have been widely utilized in plastics, electronics, furniture, and textiles as flame retardants since the 1980s, and research has indicated a significant correlation between their exposure and the risk of TC. Even so, PBDEs exposure impact on the metabolic signature for TC remains unexplored. 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 further performed by ultra-high performance liquid chromatography coupled to hybrid quadrupole-Orbitrap MS. In the partial correlation analysis, the 29 identified metabolites were correlated with PBDEs exposure (P < 0.05). In addition, PBDEs disrupted the metabolism of glycerophospholipids, sphingolipids, taurine, and hypotaurine, indicating that neurotransmitters, oxidative stress, and inflammation are the vulnerable pathways affected in PTC. Furthermore, (±)-octopamine and 5-hydroxyindole, both of which modulate the actions of neurotransmitters, emerged as potential disturbed metabolite markers for TC following exposure to PBDEs. This study analyzed the impact of PBDEs on PTC in terms of the metabolic changes and further explored possible biomarkers, which helped us have a deep understanding of the possible mechanism of the effects of PBDEs on TC.