Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum

Our plain-English summary of Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum, by J. Creaney, S. Sneddon, I.M. Dick, et al (Disease Markers, 2013).

The study

• Authors: J. Creaney, S. Sneddon, I.M. Dick, H. Dare, N. Boudville, A.W. Musk, S.J. Skates, B.W. Robinson
• Journal: Disease Markers
• Published: 2013;35(2):119-27
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The MSLN gene products, soluble mesothelin and megakaryocyte potentiating factor (MPF), are being investigated as biomarkers for the asbestos-related cancer malignant mesothelioma (MM). Pleural fluid biomarkers of MM can be elevated when serum levels remain normal. The aim of this study was to determine if this was true for MPF and to compare levels of mesothelin. Biomarker concentrations were compared in 66 MM patients, 39 patients with other malignancies, 37 with benign disease, 18 asbestos-exposed healthy individuals, and 53 patients with chronic kidney disease. In pleural effusions, MPF and soluble mesothelin concentrations were both significantly elevated in MM patients relative to controls. No significant difference between the area under the receiver operator curve (AUC) for MPF (0.945 ± 0.02) and mesothelin (0.928 ± 0.03) when distinguishing MM from all other causes of effusion was observed. MPF and mesothelin serum concentrations were highly correlated and of equivalent diagnostic accuracy with AUCs of 0.813 ± 0.04 and 0.829 ± 0.03, respectively. Serum levels of both markers increased with decreasing kidney function. In conclusion, MPF is elevated in the pleural effusions of MM patients similar to that of mesothelin. Mesothelin and MPF convey equivalent diagnostic information for distinguishing MM from other diseases in pleural effusions as well as serum.

In plain English

This diagnostic accuracy study from Perth, Western Australia, compared two markers made from the same gene, mesothelin and megakaryocyte potentiating factor (MPF), for detecting malignant mesothelioma (MM). Pleural effusion fluid came from 43 MM patients, 79 with other cancers and 143 with nonmalignant effusions. In this fluid, both markers were significantly higher in MM. The area under the curve (an accuracy score where 1 is perfect) for separating MM from the other patients was 0.945 (95% confidence interval 0.923 to 0.977) for MPF and 0.928 (0.890 to 0.956) for mesothelin, not a significant difference. Serum came from 66 MM patients and comparison groups including asbestos-exposed people. In serum, MPF measured with one commercial kit (MBL) scored 0.813 (0.741 to 0.872) and mesothelin 0.829 (0.759 to 0.886). A second MPF kit (IBL) scored 0.549 (0.465 to 0.630), significantly lower than both. In 121 people with chronic kidney disease, serum MPF rose as kidney function worsened. The authors concluded that the two markers convey equivalent diagnostic data in pleural effusions and serum and could be used interchangeably.

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: Diagnostic accuracy study comparing biomarker levels (MPF, measured with two commercial kits, and soluble mesothelin) in stored pleural effusion and serum samples, using ROC curves
• Who was studied: Patients at Sir Charles Gairdner Hospital, Royal Perth Hospital or the Hollywood Specialist Centre in Perth, Western Australia. Effusion samples came from 43 MM patients, 79 with non-MM malignant effusions and 143 with nonmalignant effusions. Serum samples came from 66 MM patients, 19 with lung cancer, 10 with other cancers, 18 asbestos-exposed individuals, 14 with other asbestos-related disease and 23 with benign pleural effusions. A further 121 patients had chronic kidney disease stages II to V and no previous history of malignancy.
• Exposure: Not a study of asbestos exposure levels; no fiber types are given. The study measured biomarkers: soluble mesothelin with the MESOMARK assay, and MPF with the IBL N-ERC/Mesothelin kit and the MBL Human MPF kit. One comparison group in the serum analysis was asbestos-exposed healthy individuals.
• Main results:
  • Pleural effusion MPF in MM patients was 1464 plus or minus 219 ng/mL. This was significantly higher than in patients with benign effusions (96 plus or minus 10 ng/mL) and in patients with other malignancies (210 plus or minus 23 ng/mL), p less than 0.0001.
  • Pleural effusion mesothelin in MM patients was reported in the text as 33 plus or minus 7.2 nM (Table 2 gives 35.1). This was significantly higher than in benign effusions (3 plus or minus 0.8 nM in the text) and in other malignancies (7.1 plus or minus 0.7 nM).
  • Effusion MPF did not differ significantly between benign effusions related to infection and benign effusions from other causes.
  • In effusions, the AUC for distinguishing MM from all other patients was 0.945 (95% CI 0.923 to 0.977) for MPF and 0.928 (0.890 to 0.956) for mesothelin. The difference was not significant.
  • At 95% specificity, effusion MPF sensitivity for MM was 81% (threshold 600 ng/mL) and effusion mesothelin sensitivity was 70% (threshold 20 nM).
  • Serum MPF measured with the IBL N-ERC kit in MM patients (0.16 plus or minus 0.05 ng/mL) was not significantly different from healthy and benign groups combined (0.06 plus or minus 0.02 ng/mL).
  • Serum MPF measured with the MBL kit in MM patients averaged 40.4 plus or minus 6.1 ng/mL. This was significantly higher than in healthy individuals and patients with benign conditions combined.
  • Serum AUC for distinguishing MM from all other cases was 0.549 (0.465 to 0.630) for N-ERC/MPF, 0.813 (0.741 to 0.872) for MPF (MBL kit) and 0.829 (0.759 to 0.886) for mesothelin.
  • The serum AUCs for MPF (MBL kit) and mesothelin did not differ (p = 0.623). The N-ERC/MPF AUC was significantly lower than both.
  • At 95% specificity relative to healthy or benign-disease patients (n = 55), serum sensitivity for MM was 29% for N-ERC, 52% for MPF and 61% for mesothelin.
  • Serum MPF (MBL kit) correlated significantly with serum mesothelin in the MM and comparison patients.
  • In chronic kidney disease patients, mean serum MPF in stage II (16.5 plus or minus 1.8 ng/mL) was significantly lower than in stages III, IV and V.
  • 70 of 121 chronic kidney disease patients (58%) had serum MPF above 30 ng/mL.
• The authors' conclusion: The authors concluded that mesothelin and MPF convey equivalent diagnostic data in pleural effusions and serum, and could be used interchangeably in a clinical setting.
• Limitations the authors state:
  • The authors raised the technical possibility that both assays may be detecting the same uncleaved MPF-mesothelin precursor protein. They noted that this question was under investigation.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Biomarker, Mesothelioma, Pleural Effusion.

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