93 POSTER Phase I assessment of mechanistic pharmacodynamic biomarkers for MLN8054, a small-molecule inhibitor of Aurora A kinase

Abstract

An early and reliable blood test is one deficiency in diagnosis of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF) and mesothelin variants (MSLN), members of the mesothelin gene family, have been studied as candidate serum markers for MPM. We developed a novel enzyme-linked immunosorbent assay (ELISA) system to compare the diagnostic efficacy of MPF and MSLN in MPM and control groups.MPF and MSLN were assayed with ELISA in 27 consecutive MPM patients and 129 controls including patients with lung cancer and asymptomatic asbestos-exposed subjects.Statistically significant elevation of serum MPF and MSLN levels was noted in MPM patients in comparison with every control group. The area under the receiver operating characteristic curve (AUC) was calculated for differentiation of MPM and lung cancer, healthy asbestos-exposed subjects, and healthy adults. While the AUC for serum MPF was 0.879, cut-off = 19.1 ng/ml (sensitivity = 74.1%, specificity = 90.4%), the AUC for serum MSLN was 0.713, cut-off = 93.5 ng/ml (sensitivity = 59.3%, specificity = 86.2%). Comparison between AUC for MPF and MSLN values shows that MPF is significantly superior to MSLN (p = 0.025). Finally, there was a significant correlation between MPF and MSLN values for MPM (Pearson's correlation coefficient = 0.77; p < 0.001).These findings suggest that diagnostic value of MPF for MPM was better than that of MSLN although both markers showed almost equal specificity for MPM.