Comparative proteomic analysis in serum of former uranium miners with and without radon induced squamous lung cancer

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.