Helmig Simone, Lochnit Günter, Schneider Joachim
1Institute and Outpatient Clinic for Occupational and Social Medicine, Justus-Liebig-University Giessen, Aulweg 129, D-35392, Giessen, Germany.
2Institute of Biochemistry, Friedrichstraße 24, Justus-Liebig-University Giessen, D-35392, Giessen, Germany.
J Occup Med Toxicol. 2019 Mar 15;14:9. doi: 10.1186/s12995-019-0228-y. eCollection 2019.
Former uranium miners of the Wismut Company, East Germany, have been exposed to ionizing radiation from radon decay products and therefore were at high risk for lung cancer. Since histological types of cancer in the so called Wismut cohort revealed an association of high radon exposure with a higher relative frequency of squamous cell carcinoma (SqCC), we used comparative proteomic analysis to identify differentially expressed proteins in serum exposed uranium miners with SqCC.
Pooled sera of exposed former uranium miners without lung disease and pooled sera of former uranium miners with SqCC were analysed by 2-D gel electrophoresis. MALDI-TOF-MS was performed from reproducable, significantly, at least 5-fold up-regulated protein spots. Proteins were identified by MASCOT peptide mass fingerprint search. Additionally a receiver operating characteristic curve for CYFRA 21-1 was created.
The protein spots were identified as Keratin 10 (K10), Keratin 1 (K1), complement factor H (CFH) and a haptoglobin (Hpt) fragment. The sensitivity for CYFRA 21-1 reveals 60% at a specifity of 95 and 80% at a specifity of 80%. Plotting the sensitivity against specifity reveals an AUC of 0.88.
In SqCC Keratin 10 and 1 were strongly induced. This was associated with CYFRA 21-1, confirming the cytokeratin fragment as a tumormarker.
东德的威斯特姆公司(Wismut Company)的前铀矿工人曾暴露于氡衰变产物的电离辐射中,因此患肺癌的风险很高。由于在所谓的威斯特姆队列中癌症的组织学类型显示高氡暴露与鳞状细胞癌(SqCC)的相对较高频率之间存在关联,我们使用比较蛋白质组学分析来鉴定患有SqCC的暴露铀矿工人血清中差异表达的蛋白质。
通过二维凝胶电泳分析未患肺病的暴露前铀矿工人的混合血清和患有SqCC的前铀矿工人的混合血清。对可重复的、显著上调至少5倍的蛋白质斑点进行基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)分析。通过MASCOT肽质量指纹搜索鉴定蛋白质。此外,还创建了细胞角蛋白片段21-1(CYFRA 21-1)的受试者工作特征曲线。
鉴定出的蛋白质斑点为角蛋白10(K10)、角蛋白1(K1)、补体因子H(CFH)和一个触珠蛋白(Hpt)片段。CYFRA 21-1的敏感性在特异性为95%时为60%,在特异性为80%时为80%。绘制敏感性与特异性的关系图显示曲线下面积(AUC)为0.88。
在SqCC中,角蛋白10和1被强烈诱导。这与CYFRA 21-1相关,证实细胞角蛋白片段为肿瘤标志物。