Elevated Serum Megakaryocyte Potentiating Factor as a Predictor of Poor Survival in Patients with Mesothelioma and Primary Lung Cancer

Our plain-English summary of Elevated Serum Megakaryocyte Potentiating Factor as a Predictor of Poor Survival in Patients with Mesothelioma and Primary Lung Cancer, by Y. Yu, B.M. Ryan, A. Thomas, et al (The Journal of Applied Laboratory Medicine, 2018).

The study

• Authors: Y. Yu, B.M. Ryan, A. Thomas, B. Morrow, J. Zhang, Z. Kang, A. Zingone, M. Onda, R. Hassan, I. Pastan, L. Cao
• Journal: The Journal of Applied Laboratory Medicine
• Published: 2018;3(2):166-177
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: There is an urgent need for a companion assay to work with mesothelin-targeted therapeutic agents and for noninvasive and accurate prognostication of malignant mesothelioma (MM) patients. We report the development and validation of a blood-based assay for megakaryocyte potentiating factor (MPF) and the evaluation of its effectiveness for prognosis in MM and lung cancer patients.

Methods: Using electrochemiluminescence technology, we developed a sensitive MPF assay and performed both analytical and clinical validations. Further, the effectiveness of the MPF assay in predicting prognosis was evaluated for 95 MM and 272 lung cancer patients.

Results: We performed comprehensive analytical and clinical validation, including precision and accuracy, interference, preanalytical variables, sensitivity, and specificity for mesothelioma. In MM patients, increased serum MPF is a predictor of poor survival with a hazard ratio (HR) = 2.46 (log-rank P = 0.003; n = 95). In refractory MM patients, increased MPF is a strong predictor of poor outcome with an HR = 6.12 (log-rank P = 0.0007; n = 57). In a lung cancer patient cohort, increased MPF is a predictor of poor survival, with an HR = 1.57 (log-rank P = 0.003; n = 272).

Conclusions: The MPF assay has robust technical characteristics, with strong analytic and clinical validation. Clinical studies indicate that increased serum MPF is a predictor of poor survival for MM patients, throughout the course of the disease. Increased MPF is also associated with poor overall survival for patients with newly diagnosed lung cancer.

In plain English

The authors developed and tested a blood test for megakaryocyte potentiating factor (MPF), a protein released from the mesothelin gene product, and asked whether high levels were linked to shorter survival. Asbestos exposure was not studied. Serum from 95 malignant mesothelioma patients was compared with serum from 56 healthy donors, whose results set a cutoff of 1.2 ng/mL. Mean MPF was 10.5 ng/mL in the patients and 0.51 ng/mL in the donors. At the cutoff the test flagged 66.3% of patients, and the authors said it would not be adequate for diagnosing mesothelioma. Median survival was 24.0 months for patients with high MPF and 92.3 months for those with low MPF. After adjustment, the hazard ratio for high MPF was 2.06 (95% CI 1.01 to 4.20). In 272 African-American lung cancer patients, high MPF was linked to worse survival (adjusted hazard ratio 1.50, 95% CI 1.04 to 2.18). The authors concluded that high serum MPF predicts poor survival in mesothelioma throughout the disease and is associated with poor survival in newly diagnosed lung cancer. They called for confirmation in further studies.

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 and validation of a blood test (electrochemiluminescence immunoassay for MPF), with survival analyses in a mesothelioma patient group and a lung cancer patient group
• Who was studied: 95 malignant mesothelioma patients (26 peritoneal, 68 pleural, 1 testicular; 57 previously treated) with samples collected June 2008 to January 2016 at the NIH Clinical Center, USA; 56 healthy blood donors; and 272 self-identified African-American lung cancer patients from the NCI-Maryland lung cancer study
• Exposure: No asbestos or fiber exposure was examined. The factor studied was the serum MPF level, classed as high or low using a cutoff of 1.2 ng/mL set from the healthy donors (mean plus 3 SD).
• Main results:
  • Mean serum MPF was 10.5 ng/mL (95% CI 5.75 to 15.27) in the 95 mesothelioma patients and 0.51 ng/mL (95% CI 0.45 to 0.57) in the 56 healthy donors (P = 0.002).
  • Mean MPF was 21.8 ng/mL in peritoneal mesothelioma patients (n = 26) and 6.4 ng/mL in pleural mesothelioma patients (n = 68) (P = 0.004).
  • At the 1.2 ng/mL cutoff, the test had a sensitivity of 66.3% and a selectivity of 98.2% in the 95 mesothelioma patients tested. The ROC area under the curve was 87.3% (95% CI 81.5% to 93.1%).
  • In all 95 mesothelioma patients, median survival was 24.0 months with high MPF and 92.3 months with low MPF. The unadjusted hazard ratio was 2.46 (95% CI 1.33 to 4.53; P = 0.004).
  • After adjustment for age, sex, histology and tumor site, the hazard ratio for high MPF in all mesothelioma patients was 2.06 (95% CI 1.01 to 4.20; P = 0.046).
  • In pleural mesothelioma patients, high MPF had a hazard ratio of 2.19 (95% CI 1.23 to 3.91; P = 0.014).
  • In the 57 previously treated mesothelioma patients, the unadjusted hazard ratio for high MPF was 6.12 (95% CI 1.86 to 20.07; P = 0.003). The adjusted hazard ratio was 3.97 (95% CI 0.88 to 17.91; P = 0.073), which the authors called of borderline significance.
  • In 272 African-American lung cancer patients, 83 (30.5%) had high MPF. The unadjusted hazard ratio was 1.57 (95% CI 1.14 to 2.17; P = 0.005). After adjustment for age, sex, smoking status, pack-years, stage and histology, it was 1.50 (95% CI 1.04 to 2.18; P = 0.029).
  • In lung cancer patients, after adjustment, high MPF was associated with poor prognosis in adenocarcinoma (HR 1.39; 95% CI 1.05 to 1.85; P = 0.020) and in squamous cell carcinoma (HR 1.44; 95% CI 1.04 to 2.00; P = 0.029).
• The authors' conclusion: The authors concluded that increased serum MPF is a predictor of poor survival for malignant mesothelioma patients throughout the course of the disease, and is associated with poor overall survival in patients with newly diagnosed lung cancer.
• Limitations the authors state:
  • The authors attributed the borderline result in previously treated mesothelioma patients to the small sample size (57 patients).
  • The authors said the mesothelioma finding should be reconfirmed in an independent sample set.
  • The authors said a confirmatory study is needed for lung cancer.
  • The lung cancer group was African-American only. The authors said the test's usefulness in people of European and Asian descent should be tested.
  • The authors stated the MPF test would not be adequate for diagnosing mesothelioma.

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: Mesothelioma, Lung Cancer, Mesothelin, Malignant Mesothelioma, Prognosis, Hazard Ratio, Overall Survival.

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• Effectiveness of serum megakaryocyte potentiating factor in evaluating the effects of chrysotile and its heated products on respiratory organs — A. Takata, H. Yamauchi, et al. (2011)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor — K. Hollevoet, K. Nackaerts, et al. (2012)
• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma — C. Jiménez-Ramírez, S. Casjens, et al. (2019)

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