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The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor

Kevin Hollevoet UGent, Kristiaan Nackaerts, Olivier Thas UGent, Joël Thimpont, Paul Germonpré, Paul De Vuyst, Lionel Bosquée, Catherine Legrand, Eliane Kellen and Yoshiro Kishi, et al. (2012) CHEST. 141(2). p.477-484
abstract
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 fi ltration 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 signifi cantly 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 signifi cantly 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 signifi cant 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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author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
REFERENCE RANGES, SERUM MESOTHELIN, OVARIAN-CANCER, MALIGNANT PLEURAL MESOTHELIOMA, GLOMERULAR-FILTRATION-RATE, PROSTATE-SPECIFIC ANTIGEN, TUMOR-MARKER, LUNG-CANCER, POPULATION, EFFUSIONS
journal title
CHEST
Chest
volume
141
issue
2
pages
477 - 484
Web of Science type
Article
Web of Science id
000299917900027
JCR category
RESPIRATORY SYSTEM
JCR impact factor
5.854 (2012)
JCR rank
4/50 (2012)
JCR quartile
1 (2012)
ISSN
0012-3692
DOI
10.1378/chest.11-0129
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2044317
handle
http://hdl.handle.net/1854/LU-2044317
date created
2012-02-24 14:52:39
date last changed
2012-05-08 10:40:09
@article{2044317,
  abstract     = {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 fi ltration 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 signifi cantly 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 signifi cantly 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 signifi cant 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.},
  author       = {Hollevoet, Kevin and Nackaerts, Kristiaan  and Thas, Olivier and Thimpont, Jo{\"e}l and Germonpr{\'e}, Paul  and De Vuyst, Paul  and Bosqu{\'e}e, Lionel and Legrand, Catherine  and Kellen, Eliane and Kishi, Yoshiro and Delanghe, Joris and Van Meerbeeck, Jan},
  issn         = {0012-3692},
  journal      = {CHEST},
  keyword      = {REFERENCE RANGES,SERUM MESOTHELIN,OVARIAN-CANCER,MALIGNANT PLEURAL MESOTHELIOMA,GLOMERULAR-FILTRATION-RATE,PROSTATE-SPECIFIC ANTIGEN,TUMOR-MARKER,LUNG-CANCER,POPULATION,EFFUSIONS},
  language     = {eng},
  number       = {2},
  pages        = {477--484},
  title        = {The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor},
  url          = {http://dx.doi.org/10.1378/chest.11-0129},
  volume       = {141},
  year         = {2012},
}

Chicago
Hollevoet, Kevin, Kristiaan Nackaerts, Olivier Thas, Joël Thimpont, Paul Germonpré, Paul De Vuyst, Lionel Bosquée, et al. 2012. “The Effect of Clinical Covariates on the Diagnostic and Prognostic Value of Soluble Mesothelin and Megakaryocyte Potentiating Factor.” Chest 141 (2): 477–484.
APA
Hollevoet, K., Nackaerts, K., Thas, O., Thimpont, J., Germonpré, P., De Vuyst, P., Bosquée, L., et al. (2012). The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor. CHEST, 141(2), 477–484.
Vancouver
1.
Hollevoet K, Nackaerts K, Thas O, Thimpont J, Germonpré P, De Vuyst P, et al. The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor. CHEST. 2012;141(2):477–84.
MLA
Hollevoet, Kevin, Kristiaan Nackaerts, Olivier Thas, et al. “The Effect of Clinical Covariates on the Diagnostic and Prognostic Value of Soluble Mesothelin and Megakaryocyte Potentiating Factor.” CHEST 141.2 (2012): 477–484. Print.