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Diagnostic Performance of Soluble Mesothelin and Megakaryocyte Potentiating Factor in Mesothelioma

¹ Department of Respiratory Medicine, and ⁹ Department of Clinical Chemistry, Ghent University Hospital, Ghent; ² Department of Respiratory Medicine, University Hospital Gasthuisberg, Leuven; ³ Occupational Diseases Fund, Brussels; ⁴ Department of Respiratory Medicine, Antwerp University Hospital, Antwerp; ⁵ Department of Respiratory Medicine, CHU Sart Tilman, Liège; ⁶ Department of Respiratory Medicine, Erasme Hospital ULB, Brussels; ⁷ Institut de Statistique, Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and ⁸ Department of Research and Development, Ina Institute, Medical & Biological Laboratories Co. Ltd., Nagano, Japan

Correspondence and requests for reprints should be addressed to Kevin Hollevoet, M.Sc., Ghent University Hospital, Department of Respiratory Medicine 7K12IE, De Pintelaan 185, 9000 Ghent, Belgium. E-mail: kevin.hollevoet{at}ugent.be

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.

Key Words: ERC • soluble mesothelin related protein • biomarkers • pleural malignancy • sensitivity

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), another fraction of the mesothelin precursor protein, is potentially more sensitive, yet lacks validation. What This Study Adds to the Field We compared MPF with SM in a prospective multicenter study and found that both MPM markers have an equivalent diagnostic performance.