title: The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor.
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 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.
authors: Department of Respiratory Medicine, Ghent University Hospital, Ghent.
authors: Kevin
authors: K
authors: Hollevoet
authors: Department of Respiratory Medicine, University Hospital Gasthuisberg, Leuven.
authors: Kristiaan
authors: K
authors: Nackaerts
authors: Department of Applied Mathematics, Biometrics and Process Control, Ghent University, Ghent.
authors: Olivier
authors: O
authors: Thas
authors: Occupational Diseases Fund, Erasme Hospital ULB, Brussels.
authors: Joël
authors: J
authors: Thimpont
authors: Department of Respiratory Medicine, Antwerp University Hospital, Antwerp.
authors: Paul
authors: P
authors: Germonpré
authors: Department of Respiratory Medicine, Erasme Hospital ULB, Brussels.
authors: Paul
authors: P
authors: De Vuyst
authors: Department of Respiratory Medicine, Louvain-la-Neuve, Belgium.
authors: Lionel
authors: L
authors: Bosquée
authors: CHU Sart Tilman, Liège; and Institut de Statistique, Biostatistique et Sciences Actuarielles, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
authors: Catherine
authors: C
authors: Legrand
authors: Center for Cancer Prevention, University Hospital Gasthuisberg, Leuven.
authors: Eliane
authors: E
authors: Kellen
authors: Department of Research and Development, Ina Institute, Medical and Biological Laboratories, Co Ltd, Nagano, Japan.
authors: Yoshiro
authors: Y
authors: Kishi
authors: Department of Clinical Chemistry, Ghent University Hospital, Ghent.
authors: Joris R
authors: JR
authors: Delanghe
authors: Department of Respiratory Medicine, Ghent University Hospital, Ghent. Electronic address: jan.vanmeerbeeck@ugent.be.
authors: Jan P
authors: JP
authors: van Meerbeeck
mesh_terms: D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D016014:Linear Models; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000097:blood* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; D000090204:Mesothelin