Wang Jun, Betancourt Angela, Jenkins Sarah, Biro Frank, Pinney Susan M, Chen Dongquan, Russo Jose, Lamartiniere Coral A
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, USA.
Division of Adolescent Medicine, Children's Hospital Medical Center, USA.
MOJ Proteom Bioinform. 2015;2(2):44-57. doi: 10.15406/mojpb.2015.02.00040. Epub 2015 Mar 10.
Children exposed to endocrine disruptors are hypothesized to be susceptible for cancer development later in life. Identifying functional biomarkers of specific exposures may indicate predisposition for this disease. The objectives of this study were to identify protein biomarkers of 1) effect and 2) susceptibility for cancer from the blood of girls exposed to select environmental chemicals. In prepubertal girls, urine concentrations of bisphenol A (BPA), genistein, mono-ethyl hexylphthalate (MEHP) and mono-benzyl phthalate (MBzP) were used to identify girls in the top quintile of exposure for each of these environmental chemicals, and age-matched prepubertal girls with urine analyte concentrations below the median. Blood samples of these girls were depleted of the seven most abundant proteins using human-specific affinity spin columns. Using isobaric Tandem Mass Tags and quantitative mass spectrometry (TMT-MS), 51, 34, 57 and 47 differentially expressed proteins were identified from the blood of prepubertal girls with high urine concentrations of BPA, genistein, MEHP and MBzP, respectively, compared to controls. The data demonstrates the potential of proteomic technology to not only provide biomarkers of effect from aminimally invasive source of biological material, blood, but to identify protein molecules that are intimately involved in the pathobiology of cancer. The differentially regulated cancer associated proteins in girls with high concentrations of BPA and genistein are consistent with reported roles of BPA in carcinogenesis and of genistein in mammary cancer prevention, respectively.
有假说认为，接触内分泌干扰物的儿童在日后生活中患癌症的易感性会增加。识别特定暴露的功能性生物标志物可能预示着患这种疾病的倾向。本研究的目的是从接触特定环境化学物质的女孩血液中识别出1）效应和2）癌症易感性的蛋白质生物标志物。在青春期前女孩中，双酚A（BPA）、染料木黄酮、单-乙基己基邻苯二甲酸酯（MEHP）和单-苄基邻苯二甲酸酯（MBzP）的尿液浓度被用于识别每种环境化学物质暴露处于最高五分位数的女孩，以及尿液分析物浓度低于中位数的年龄匹配的青春期前女孩。使用人特异性亲和旋转柱去除这些女孩血液样本中七种最丰富的蛋白质。使用等压串联质量标签和定量质谱（TMT-MS），与对照组相比，分别从尿液中BPA、染料木黄酮、MEHP和MBzP浓度高的青春期前女孩血液中鉴定出51、34、57和47种差异表达蛋白。数据表明蛋白质组学技术不仅有潜力从生物材料血液这种微创来源提供效应生物标志物，还能识别与癌症病理生物学密切相关的蛋白质分子。BPA和染料木黄酮浓度高的女孩中差异调节的癌症相关蛋白分别与报道的BPA在致癌作用中的作用以及染料木黄酮在预防乳腺癌中的作用一致。
