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RATIONALE: Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation. OBJECTIVES: To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with SM. METHODS: A total of 507 participants were enrolled in six cohorts: healthy control subjects (n = 101), healthy asbestos-exposed individuals (n = 89), and patients with benign asbestos-related disease (n = 123), benign respiratory disease (n = 46), lung cancer (n = 63), and MPM (n = 85). Sera were analyzed for SM and MPF levels using the Mesomark and Human MPF ELISA kit, respectively. MEASUREMENTS AND MAIN RESULTS: SM and MPF levels differed significantly between patients with MPM and participants from each other cohort (P < 0.001). Receiver operating characteristics curve analysis did not reveal a significant difference between both markers in area under curve (AUC) for distinguishing MPM from all cohorts jointly (SM = 0.871, MPF = 0.849; P = 0.28). At 95% specificity, SM and MPF had a sensitivity of 64% (cutoff = 2.00 nmol/L) and 68% (cutoff = 12.38 ng/ml), respectively. Combining both markers did not improve the diagnostic performance. CONCLUSIONS: In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance. [ABSTRACT FROM AUTHOR]

Abstract Background Plasma transforming growth factor β1 (TGFβ1 ) levels are elevated in patients with lung cancer. As TGFβ1 is mainly found in platelets and as nonmalignant pulmonary diseases (NMPD) are frequently associated with lung cancer, we investigated the potential contribution of platelet degranulation and/or of a concomitant NMPD to the increased plasma levels of TGFβ1 reported in patients with lung cancer. Materials and Methods Blood samples were collected in duplicate from 30 healthy subjects, 14 patients suffering from NMPD and 37 patients with lung cancer. The platelet count was determined and the samples were processed to obtain plasma. One sample was collected in EDTA (EDTA plasma) and the other in a mixture inhibiting platelet degranulation (PIM plasma). TGFβ1 concentrations and β-thromboglobulin (βTG) levels, an index of platelet degranulation, were measured in both plasma samples. Results TGFβ1 and βTG plasma levels measured in PIM plasma were lower than those obtained in EDTA plasma. With respect to PIM plasma, both TGFβ1 and βTG levels were higher in patients with lung cancer than those with NMPD and in healthy individuals. In patients with NMPD, only TGFβ1 levels were increased as compared to healthy controls, βTG levels being similar. Conclusion Methods for collecting and processing blood samples are critical in determining reliable circulating TGFβ1 levels. Increased TGFβ1 plasma levels observed in patients with lung cancer are related, at least partly, to concomitant NMPD and also to platelet degranulation as proved by increased βTG levels. [ABSTRACT FROM AUTHOR]