A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma.
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, MPF34-288, 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 MPF34-288fragment 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 MPF34-288and mesothelin displayed an improved ROC performance (AUC = 0.80). The MPF34-288ELISA could be a cost-effective and minimal-invasive contribution to support a diagnosis of mesothelioma, especially in regions with a limited medical care.
IPA - Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum, Germany.
Irina
I
Raiko
IPA - Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum, Germany. Electronic address: rihs@ipa-dguv.de.
Hans-Peter
HP
Rihs
IPA - Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum, Germany.
Jan
J
Gleichenhagen
IPA - Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum, Germany.
Ingrid
I
Sander
Lungenklinik Heckeshorn, HELIOS Clinic Emil von Behring, Berlin, Germany.
Jens
J
Kollmeier
IPA - Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum, Germany.
Martin
M
Lehnert
IPA - Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum, Germany.
Thomas
T
Brüning
IPA - Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum, Germany.
Georg
G
Johnen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000302:isolation & purification; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood* / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D012372:ROC Curve; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology
D000906:Antibodies; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; D010455:Peptides; D011994:Recombinant Proteins; D000090204:Mesothelin
Biomarker; Diagnostic; Megakaryocyte potentiating factor; Mesothelioma