Chest

Chest

Volume 141, Issue 2, February 2012, Pages 477-484
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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 Factor

https://doi.org/10.1378/chest.11-0129Get rights and content

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.

Section snippets

Participants

Between June 2004 and 2010, consecutive individuals were recruited prospectively in a multicenter study. Control subjects included five cohorts: (1) healthy individuals, aged 50 years or older, without reported asbestos exposure; (2) individuals with documented asbestos exposure; and patients with (3) a benign non-asbestos-related respiratory condition, (4) lung cancer, and (5) a nonrespiratory epithelial cancer. Cases included patients with histologically proven mesothelioma of the pleura.

Participant Characteristics

A total of 594 individuals were included: 106 patients with histologically proven malignant pleural mesothelioma and 488 control subjects including 101 healthy and 215 asbestos-exposed individuals, 78 patients with a benign non-asbestos-related respiratory disease, 69 with a lung cancer, and 25 with a nonrespiratory epithelial cancer (Table 1). All participants were white or other, and none was black. In the cohort of asbestos-exposed individuals, 71 had pleural plaques, 39 diffuse pleural

Discussion

SM and MPF are among the best available serum biomarkers of mesothelioma, and might serve as an adjunct in the different fields of mesothelioma management. This study evaluated to what extent clinical covariates affect SM and MPF results and should be accounted for in the further validation and clinical application of both biomarkers.

We reported recently that SM and MPF are highly correlated, and have an equivalent diagnostic accuracy.4 In addition, the present study found that the serum levels

Conclusions

In conclusion, 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 recorded routinely. Approaches to account for these covariates require further validation, as does the prognostic value of SM and MPF.

Acknowledgments

Author contributions: Drs Hollevoet and van Meerbeeck had full access to all the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Hollevoet: contributed to the conception and design of the study, recruitment of study participants and collection of clinical data, setup of the statistical design of the study, performance of the laboratory work, data analysis and interpretation, drafting of the manuscript, and revision and approval

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    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).

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    Copyright © 2012 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.