Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma

Am J Respir Crit Care Med. 2010 Mar 15;181(6):620-5. doi: 10.1164/rccm.200907-1020OC. Epub 2010 Jan 14.

Abstract

Rationale: Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation.

Objectives: To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with SM.

Methods: A total of 507 participants were enrolled in six cohorts: healthy control subjects (n = 101), healthy asbestos-exposed individuals (n = 89), and patients with benign asbestos-related disease (n = 123), benign respiratory disease (n = 46), lung cancer (n = 63), and MPM (n = 85). Sera were analyzed for SM and MPF levels using the Mesomark and Human MPF ELISA kit, respectively.

Measurements and main results: SM and MPF levels differed significantly between patients with MPM and participants from each other cohort (P < 0.001). Receiver operating characteristics curve analysis did not reveal a significant difference between both markers in area under curve (AUC) for distinguishing MPM from all cohorts jointly (SM = 0.871, MPF = 0.849; P = 0.28). At 95% specificity, SM and MPF had a sensitivity of 64% (cutoff = 2.00 nmol/L) and 68% (cutoff = 12.38 ng/ml), respectively. Combining both markers did not improve the diagnostic performance.

Conclusions: In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • GPI-Linked Proteins
  • Humans
  • Male
  • Membrane Glycoproteins / blood*
  • Mesothelioma / blood*
  • Mesothelioma / diagnosis*
  • Middle Aged
  • Pleural Neoplasms / blood*
  • Prospective Studies
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • Membrane Glycoproteins
  • mesothelin