title: Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study.
abstract: BACKGROUND
  Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study aims to examine the longitudinal behavior of SM and MPF in controls to gain insight in the optimal use of these biomarkers in screening.
  
  
  METHODS
  Asbestos-exposed individuals, with no malignant disease at inclusion, were surveilled for 2 years with annual measurements of SM and MPF. Fixed thresholds were set at 2.10 nmol/L for SM and 13.10 ng/ml for MPF. Longitudinal biomarker analysis, using a random intercept model, estimated the association with age and glomerular filtration rate (GFR), and the intraclass correlation. The latter represents the proportion of total biomarker variance accounted for by the between-individual variance.
  
  
  RESULTS
  A total of 215 participants were included, of whom 179 and 137 provided a second sample and third sample, respectively. Two participants with normal SM and MPF levels presented afterward with mesothelioma and lung cancer, respectively. Participants with elevated biomarker levels were typically older and had a lower GFR. During follow-up, biomarker levels significantly increased. Longitudinal analysis indicated that this was in part due to aging, while changes in GFR had a less pronounced effect on serial biomarker measurements. SM and MPF had a high intraclass correlation of 0.81 and 0.78, respectively, which implies that a single biomarker measurement and fixed threshold are suboptimal in screening.
  
  
  CONCLUSIONS
  The longitudinal behavior of SM and MPF in controls indicates that a biomarker-based screening approach can benefit from the incorporation of serial measurements and individual-specific screening rules, adjusted for age and GFR. Large-scale validation remains nevertheless mandatory to elucidate whether such an approach can improve the early detection of mesothelioma.
authors.affiliation: Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. kevin.hollevoet@ugent.be
authors.forename: Kevin
authors.initials: K
authors.lastname: Hollevoet
authors.forename: Joris
authors.initials: J
authors.lastname: Van Cleemput
authors.forename: Joël
authors.initials: J
authors.lastname: Thimpont
authors.forename: Paul
authors.initials: P
authors.lastname: De Vuyst
authors.forename: Lionel
authors.initials: L
authors.lastname: Bosquée
authors.forename: Kristiaan
authors.initials: K
authors.lastname: Nackaerts
authors.forename: Paul
authors.initials: P
authors.lastname: Germonpré
authors.forename: Stijn
authors.initials: S
authors.lastname: Vansteelandt
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kishi
authors.forename: Joris R
authors.initials: JR
authors.lastname: Delanghe
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Meerbeeck
mesh_terms: D000368:Aged; D001194:Asbestos / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood / Q000175:diagnosis*; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D010997:Pleural Neoplasms / Q000097:blood / Q000175:diagnosis*; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; D001194:Asbestos; D000090204:Mesothelin