A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma

Biochem Biophys Res Commun. 2017 Apr 29;486(2):526-532. doi: 10.1016/j.bbrc.2017.03.077. Epub 2017 Mar 19.

Abstract

Malignant mesothelioma (MM) is a fatal disease mostly associated with asbestos exposure and difficult to detect by non-invasive methods. This study aimed to use recombinant fragments of the megakaryocyte potentiating factor (MPF) for the development of cost-effective MPF ELISAs. Three polypeptides spanning the MPF region (MPF1-148, MPF 34-288, MPF/MSLN254-400) were produced in E.coli as maltose-binding protein hybrids. After isolation, Factor Xa digest, and purification, the polypeptides were used for the generation of rabbit antibodies and development of ELISAs. Forty-one MM patients with known histological subtype before tumor-specific treatment and 70 asbestos-exposed individuals free of any cancer were matched according to age, gender, and smoking. Plasma of all subjects was tested with the three newly developed polyclonal antibody-based ELISAs and a commercial mesothelin assay (MESOMARK™). The latter differentiated patients (median concentration 1.95 nM) from controls (median 1.07 nM, p < 0.0001) and showed an area under curve (AUC) of 0.77 in receiver operating characteristics (ROC) analysis. Of the MPF variants, exclusively the ELISA based on antibodies against the MPF34-288 fragment displayed significantly (p = 0.0002) higher values in patients than in controls (median 1.61 nM versus 0.88 nM; AUC = 0.72). The combination of the MPF34-288 and mesothelin displayed an improved ROC performance (AUC = 0.80). The MPF34-288 ELISA could be a cost-effective and minimal-invasive contribution to support a diagnosis of mesothelioma, especially in regions with a limited medical care.

Keywords: Biomarker; Diagnostic; Megakaryocyte potentiating factor; Mesothelioma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antibodies / chemistry
  • Antibodies / isolation & purification
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / immunology
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Female
  • GPI-Linked Proteins / blood*
  • GPI-Linked Proteins / immunology
  • HeLa Cells
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Male
  • Mesothelin
  • Mesothelioma / blood
  • Mesothelioma / diagnosis*
  • Mesothelioma / immunology
  • Mesothelioma / pathology
  • Mesothelioma, Malignant
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / immunology*
  • Peptides / metabolism
  • ROC Curve
  • Rabbits
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / immunology

Substances

  • Antibodies
  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • MSLN protein, human
  • Peptides
  • Recombinant Proteins
  • Mesothelin