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

Our plain-English summary of A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma, by I. Raiko, H.P. Rihs, J. Gleichenhagen, et al (Biochemical and Biophysical Research Communications, 2017).

The study

• Authors: I. Raiko, H.P. Rihs, J. Gleichenhagen, I. Sander, J. Kollmeier, M. Lehnert, T. Brüning, G. Johnen
• Journal: Biochemical and Biophysical Research Communications
• Published: 2017;486(2):526-532
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

In plain English

The authors raised rabbit antibodies against three fragments of the blood protein megakaryocyte potentiating factor (MPF) and built three blood tests (ELISAs) meant to be affordable. They tested plasma from 41 mesothelioma patients in Berlin, taken before surgery, chemotherapy or radiation therapy, and from 70 matched asbestos-exposed people without cancer. Two of the tests showed no significant difference between the groups. The MPF34-288 test gave a median of 1.61 nM in patients versus 0.88 nM in controls (p = 0.0002). Its AUC (a measure of how well a test separates groups) was 0.72 (95% CI 0.61 to 0.82). The commercial MESOMARK mesothelin test gave medians of 1.95 nM in patients and 1.07 nM in controls, with an AUC of 0.77 (95% CI 0.67 to 0.86). Combining the two tests gave an AUC of 0.80 (95% CI 0.71 to 0.89). MPF levels in the four sarcomatoid mesothelioma patients were similar to controls. The authors concluded that the MPF34-288 test could distinguish patients from controls, except sarcomatoid cases. They said the small subtype groups limit interpretation and that results need checking in larger groups.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory development of three antibody-based blood tests (ELISAs), evaluated by comparing mesothelioma patients with matched asbestos-exposed controls
• Who was studied: 41 malignant mesothelioma patients (33 males, 8 females, mean age 69 years, range 35 to 85) were recruited at the HELIOS Clinic Emil von Behring, Berlin, Germany. None had surgery, chemotherapy or radiation therapy before blood collection. Of these, 31 had epithelioid, six biphasic and four sarcomatoid mesothelioma. The controls were 70 asbestos-exposed individuals without mesothelioma or other cancers, matched by age, gender and smoking status. Study dates are not given.
• Exposure: The controls were asbestos-exposed individuals, some with benign asbestos-related diseases such as pleural plaques or asbestosis. Fiber types and exposure levels are not described. The measurement studied was blood plasma levels of MPF and mesothelin.
• Main results:
  • The ELISAs based on the MPF1-148 and MPF/MSLN254-400 fragments measured concentrations all below 2 nM, with no significant difference between patients and controls.
  • With the MPF34-288 ELISA, the median in mesothelioma patients was 1.61 nM (range 0.31 to 39.8 nM). The median in controls was 0.88 nM (range 0.38 to 6.11 nM). The difference was significant (p = 0.0002).
  • The commercial MESOMARK mesothelin assay gave a median of 1.95 nM in patients and 1.07 nM in asbestos-exposed controls (p less than 0.0001).
  • For telling patients from controls, the AUC was 0.72 (95% CI 0.61 to 0.82) for MPF34-288, 0.77 (95% CI 0.67 to 0.86) for mesothelin, and 0.80 (95% CI 0.71 to 0.89) for the two combined.
  • MPF34-288 levels in epithelioid mesothelioma (31 patients, median 1.76 nM) were significantly higher than in controls (70 controls, median 0.88 nM; p less than 0.0001).
  • MPF34-288 levels in sarcomatoid mesothelioma (4 patients, median 0.65 nM) were similar to those in controls.
  • In biphasic mesothelioma (6 patients, median 1.50 nM), the difference from controls did not reach statistical significance (p = 0.083).
• The authors' conclusion: The authors concluded that the new MPF34-288 ELISA can distinguish asbestos-exposed controls from mesothelioma patients, excluding those with the sarcomatoid subtype. They added that, after validation in a prospective study, it could be a cost-effective tool to support diagnosis.
• Limitations the authors state:
  • The small numbers of sarcomatoid (4) and biphasic (6) cases limit interpretation of the subtype results.
  • All results need to be verified in a larger, independent group of patients and matched controls.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Malignant Mesothelioma, Asbestos Exposure, Histological Subtype, Mesothelin.

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