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

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