Malignant mesothelioma cells secrete natriuretic peptides: Data and diagnostic clinical implications

Our plain-English summary of Malignant mesothelioma cells secrete natriuretic peptides: Data and diagnostic clinical implications, by V. Tsolaki, S. Zarogiannis, P. Zygoulis, et al (Respirology, 2020).

The study

• Authors: V. Tsolaki, S. Zarogiannis, P. Zygoulis, I. Kalomenidis, R. Jagirdar, D. Makris, Z. Daniil, S. Magkouta, I. Triantafyllou, J. Papanikolaou, K.I. Gourgoulianis, E. Zakynthinos
• Journal: Respirology
• Published: 2020;25(10):1060-1065
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background And Objective: Mesothelial cells and cardiomyocytes have shared embryonic mesodermal origin. Cardiomyocytes release BNP under stretch. We searched whether malignant mesothelioma cells also secrete BNP and if so, this has a meaningful impact.

Methods: Part I: Prospectively, patients with pleural lesions on CT having malignant mesothelioma effusions (MME, n = 13) were compared to patients with malignant effusions with pleural lesions (MEa, n = 14). Age-matched patients with ME without pleural lesions (MEb, n = 16) and non-malignant effusions (NME, n = 25) were analysed. Part II: Retrospectively, samples from patients with mesothelioma (n = 14), lung cancer (n = 8) or heart failure (n = 9) were used. BNP was measured in pleural fluid and blood/plasma. Part III: BNP was assessed in the culture supernatants of benign (MeT-5A) and malignant mesothelioma cell lines (M14K-epithelioid, MSTO-biphasic and ZL34-sarcomatoid) (n = 10 per cell line in three different biological replicates).

Results: In vitro, BNP concentration was significantly higher in the supernatant of all malignant cell lines than benign ones (P < 0.01), denoting BNP's production from the former. The pleural fluid to blood BNP ratio in MME was extremely high in Part I and Part II subjects (28.3 ± 12.1 and 25.9 ± 8.6, respectively) versus 1.1 ± 0.3 and 0.4 ± 0.1 in Part I ME and NME, respectively (P < 0.0001), and 0.8 ± 0.1 and 0.4 ± 0.1 in Part II ME and NME, respectively (P < 0.0001). BNP ratio ≥2.11 in Part I had 92% sensitivity and 94.5% specificity for MME (P < 0.0001).

Conclusion: BNP is secreted from malignant mesothelial cells. In clinical practice, the pleural fluid to blood BNP ratio can help in the diagnosis of malignant mesothelioma.

© 2020 Asian Pacific Society of Respirology.

In plain English

This Greek study, in three parts, asked whether malignant mesothelioma cells release B-type natriuretic peptide (BNP), a hormone usually linked to the heart, and whether this could help diagnosis. It did not study asbestos exposure. In Part I, at the University Hospital of Larissa between 2007 and 2018, the authors compared the ratio of BNP in pleural fluid to BNP in blood in 13 patients with malignant mesothelioma effusions, 30 with other malignant effusions (mostly lung cancer) and 25 with non-malignant effusions. The average ratio was 28.3 in the mesothelioma group, against about 1 or lower in the other groups. A ratio of 2.11 or more identified mesothelioma with 92% sensitivity and 94.5% specificity. Part II used stored samples from 14 mesothelioma, 8 lung cancer and 9 heart failure patients and gave similar results. In Part III, three malignant mesothelioma cell lines released more BNP than a benign mesothelial cell line. The authors called the study preliminary and small. They concluded that the ratio may help diagnosis but that the findings need further validation.

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: Three-part study: a prospective observational patient study (Part I), a retrospective study of stored biobank samples (Part II), and a laboratory cell-culture experiment (Part III)
• Who was studied: Part I: patients at the University Hospital of Larissa, Greece, January 2007 to October 2018. There were 13 with malignant mesothelioma effusions (MME), 14 with other malignant effusions with pleural lesions (MEa), 16 with malignant effusions without pleural lesions (MEb) and 25 with non-malignant effusions (NME). Part II: stored samples from Evangelismos Hospital, Athens, from 14 mesothelioma, 8 lung cancer and 9 heart failure patients. Part III: one benign mesothelial cell line (MeT-5A) and three malignant pleural mesothelioma cell lines (M14K epithelioid, MSTO biphasic, ZL34 sarcomatoid), 10 measurements each
• Exposure: The article does not study or report asbestos or other exposures. What it measured was BNP in pleural fluid, in blood or plasma, and in cell culture fluid.
• Main results:
  • Part I: the pleural fluid to blood BNP ratio was 28.3 (SEM 12.1) in malignant mesothelioma effusion patients. It was 0.98 (SEM 0.2) in MEa (p less than 0.001), 1.1 (SEM 0.3) in MEb and 0.4 in NME (both p less than 0.0001).
  • Part I: a BNP ratio of 2.11 or more identified mesothelioma patients with 92% sensitivity and 94.5% specificity (AUC 0.944, 95% CI 0.863 to 1.0). All but one mesothelioma patient had a ratio above 2; that patient's ratio was 0.3.
  • Part I: among other malignant effusions, the BNP ratio was not higher in patients whose pleural metastatic lesions were visible on chest CT than in those without visible lesions.
  • Part II: the BNP ratio was 25.9 (SEM 8.6) in the 14 mesothelioma patients, 0.8 in the 8 lung cancer patients and 0.4 in the 9 heart failure patients (both p less than 0.0001). A ratio of 2.42 had 92.9% sensitivity and 100% specificity (AUC 0.996).
  • Part III: BNP in culture fluid was 422.7 pg/mL for the epithelioid line M14K, 193.6 pg/mL for the sarcomatoid line ZL34, 38.5 pg/mL for the biphasic line MSTO and 5.0 pg/mL for the benign line MeT-5A (n = 10 for each cell line).
• The authors' conclusion: The authors concluded that, in this preliminary study, BNP is produced by malignant mesothelioma cells, as confirmed in the lab, and that the pleural fluid to blood BNP ratio can be useful for diagnosing malignant mesothelioma. They also said both the clinical and experimental findings need further validation.
• Limitations the authors state:
  • The study was preliminary, with a small number of patients in each group.
  • Few patients had pleural spread from cancers other than lung cancer, so it is unknown whether those cancers also give high BNP ratios.
  • Diagnosis was mainly based on cytology, and the exact mesothelioma subtypes of the patients were not available.
  • The authors believe that heart failure in a mesothelioma patient would lower the BNP ratio. No mesothelioma patients in the study had severe cardiac failure.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelial Cells, Mesothelioma, Lung Cancer, Epithelioid, Biphasic Mesothelioma, Sarcomatoid.

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