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Original Research: DISORDERS OF THE PLEURA |

The Effect of Clinical Covariates on the Diagnostic and Prognostic Value of Soluble Mesothelin and Megakaryocyte Potentiating FactorEffect of Covariates on Biomarker Results

Kevin Hollevoet, PhD; Kristiaan Nackaerts, MD, PhD; Olivier Thas, PhD; Joël Thimpont, MD; Paul Germonpré, MD, PhD; Paul De Vuyst, MD, PhD; Lionel Bosquée, MD; Catherine Legrand, PhD; Eliane Kellen, MD, PhD; Yoshiro Kishi, PhD; Joris R. Delanghe, MD, PhD; Jan P. van Meerbeeck, MD, PhD
Author and Funding Information

From the Department of Respiratory Medicine (Drs Hollevoet and van Meerbeeck), and the Department of Clinical Chemistry (Dr Delanghe), Ghent University Hospital; the Department of Applied Mathematics, Biometrics and Process Control (Dr Thas), Ghent University, Ghent; the Department of Respiratory Medicine (Dr Nackaerts), and The Center for Cancer Prevention (Dr Kellen), University Hospital Gasthuisberg, Leuven; the Department of Respiratory Medicine (Dr Germonpré), Antwerp University Hospital, Antwerp; Occupational Diseases Fund (Dr Thimpont), and the Department of Respiratory Medicine (Dr De Vuyst), Erasme Hospital ULB, Brussels; the Department of Respiratory Medicine (Dr Bosquée), CHU Sart Tilman, Liège; and Institut de Statistique, Biostatistique et Sciences Actuarielles (Dr Legrand), Université Catholique de Louvain, Louvain-la-Neuve, Belgium; and the Department of Research and Development (Dr Kishi), Ina Institute, Medical and Biological Laboratories, Co Ltd, Nagano, Japan.

Correspondence to: Jan van Meerbeeck, MD, PhD, Department of Respiratory Medicine 7K12IE, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium; e-mail: jan.vanmeerbeeck@ugent.be


Funding/Support: This study was supported by the Foundation Against Cancer, a Belgian foundation of public interest, and by the Emmanuel van der Schueren research grant from the Flemish League Against Cancer. In addition, Cis bio International (France) provided a research grant (to Dr van Meerbeeck) to purchase Mesomark enzyme-linked immunosorbent assays.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(2):477-484. doi:10.1378/chest.11-0129
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Background:  Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study examined the effect of clinical covariates on biomarkers levels and their diagnostic and prognostic value.

Methods:  Five hundred ninety-four participants were enrolled in a multicenter study, including 106 patients with mesothelioma and 488 control subjects. Multiple linear regression analyses were used to identify which covariates were independently associated with SM and MPF levels. The effect of these covariates on the diagnostic accuracy was evaluated with receiver operating characteristics curve analysis. In patients with mesothelioma, survival analysis was performed with Cox regression.

Results:  SM and MPF levels were independently associated with age, glomerular filtration rate (GFR), and BMI in control subjects and with GFR and tumor stage in patients with mesothelioma. The diagnostic accuracy of SM and MPF was significantly affected by the distribution of these covariates in the study population. The patients with mesothelioma were best discriminated from the control subjects with either the youngest age, the highest GFR, or the largest BMI. Furthermore, the control subjects were significantly better differentiated from stage II to IV than from stage I mesothelioma. MPF, not SM, was an independent negative prognostic factor, but only if adjusted for the biomarker-associated covariates.

Conclusions:  SM and MPF levels were affected by the same clinical covariates, which also had a significant impact on their diagnostic and prognostic value. To improve the interpretation of biomarker results, age, GFR, and BMI should be routinely recorded. Approaches to account for these covariates require further validation, as does the prognostic value of SM and MPF.

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