Multiplex Soluble Biomarker Analysis from Pleural Effusion

Our plain-English summary of Multiplex Soluble Biomarker Analysis from Pleural Effusion, by J. Javadi, K. Dobra, A. Hjerpe (Biomolecules, 2020).

The study

• Authors: J. Javadi, K. Dobra, A. Hjerpe
• Journal: Biomolecules
• Published: 2020;10(8)
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.

In plain English

This laboratory study from Karolinska University Hospital in Sweden measured ten proteins in pleural effusion (fluid that builds up around the lungs) from 118 patients. Forty-two had malignant pleural mesothelioma of the epithelioid or mixed type, 36 had metastatic adenocarcinoma, and 40 had benign effusions. The study did not measure asbestos exposure. Compared with benign fluid, mesothelioma fluid had significantly higher levels of eight proteins, including Galectin-1, Mesothelin and Osteopontin. The results section reports NRG1-β1 as significantly lower, although other parts of the article describe it as higher. Compared with adenocarcinoma, mesothelioma fluid had higher Mesothelin and Galectin-1 and lower shed Syndecan-1 (SDC-1) and MMP-7. Among mesothelioma patients, median survival was 2.6 months with high VEGF versus 18 months with low VEGF, and 2.4 months with high shed SDC-1 versus 9.6 months with low. The authors concluded that several of these proteins could be diagnostic markers and that shed SDC-1 and VEGF are prognostic markers for malignant pleural mesothelioma. They said larger studies are needed.

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 biomarker study of pleural effusion samples. Levels were compared between patient groups (t-tests), survival was analysed by Kaplan-Meier with cut-off values, and diagnostic value was assessed by ROC and logistic regression.
• Who was studied: Pleural effusions from 118 patients collected at the Department of Pathology and Cytology, Karolinska University Hospital, Sweden: 42 with malignant pleural mesothelioma (epithelioid and mixed types only), 36 with adenocarcinoma and 40 with benign effusions. Samples were taken before any treatment. Collection dates are not given.
• Exposure: No asbestos exposure was measured. The study measured levels of 10 angiogenesis-related proteins in effusion fluid (Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 and VEGF) using Luminex multiplex kits. Some results were checked by ELISA.
• Main results:
  • Luminex and ELISA measurements correlated in pleural effusions: shed SDC-1 r = 0.8, Mesothelin r = 0.6, VEGF r = 0.9 (all p = 0.0001).
  • Mesothelioma effusions (n = 42) compared with benign effusions (n = 40): Galectin-1, Mesothelin, Osteopontin, shed SDC-1, VEGF, MMP-7, HGF and TIMP-1 were significantly higher, and NRG1-β1 was significantly lower.
  • Mesothelioma effusions (n = 42) compared with adenocarcinoma effusions (n = 36): Mesothelin and Galectin-1 were significantly higher, and shed Syndecan-1 and MMP-7 were significantly lower.
  • In stepwise logistic regression, MMP-7, Mesothelin and Osteopontin were the variables with higher predictive value for distinguishing mesothelioma from metastatic adenocarcinoma.
  • Among mesothelioma patients, median survival was 2.6 months with high VEGF (above 0.7 ng/mL) versus 18 months with low VEGF (p = 0.0003).
  • Among mesothelioma patients, median survival was 2.4 months with high shed SDC-1 (above 19.28 ng/mL) versus 9.6 months with low shed SDC-1 (p = 0.03).
  • For distinguishing mesothelioma from benign effusions (ROC analysis), the highest areas under the curve were Galectin-1 0.99, NRG1-β1 0.97, Osteopontin 0.95, Mesothelin 0.94 and shed SDC-1 0.93. MMP-7 and angiopoietin-1 had no discriminative capacity.
  • In mesothelioma cases, shed SDC-1 correlated positively with HGF (r = 0.3, p = 0.02) and NRG1-b1 (r = 0.4, p = 0.001).
• The authors' conclusion: The authors concluded that Galectin-1, Mesothelin, Osteopontin, shed SDC-1, VEGF, MMP-7, HGF, TIMP-1 and NRG1-β1 could be diagnostic biomarkers for distinguishing malignant pleural mesothelioma and metastatic adenocarcinoma from benign cases, and that shed SDC-1 and VEGF are prognostic biomarkers for malignant pleural mesothelioma.
• Limitations the authors state:
  • The authors stated that further studies with larger sample sizes are needed to validate the results.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Effusion, Pleural Mesothelioma, Asbestos Exposure, Prognosis, Dyspnea, Pleural Cavity, Histopathology.

Related studies

• Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma — F. Mundt, H.J. Johansson, et al. (2014)
• Profile of soluble factors in pleural effusions predict prognosis in mesothelioma — I.M. Dick, Y.C.G. Lee, et al. (2022)
• Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion — J. Javadi, A. Görgens, et al. (2021)
• Characterization of soluble PD-L1 in pleural effusions of mesothelioma patients: potential implications in the immune response and prognosis — R. Carosio, V. Fontana, et al. (2021)
• Diagnostic value of soluble mesothelin-related peptides in pleural effusion for malignant pleural mesothelioma: An updated meta-analysis — R. Gao, F. Wang, et al. (2019)
• Utility of HBME-1 immunostaining in serous effusions — V. Ascoli, C. Carnovale-Scalzo, et al. (1997)

Browse more research in Biomolecules, or return to medical research.