Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis

Our plain-English summary of Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis, by P. Smeele, S.M. d'Almeida, C. Meiller, et al (Molecular Cancer, 2018).

The study

• Authors: P. Smeele, S.M. d'Almeida, C. Meiller, A.L. Chéné, C. Liddell, L. Cellerin, F. Montagne, S. Deshayes, S. Benziane, M.C. Copin, P. Hofman, F. Le Pimpec-Barthes, H. Porte, A. Scherpereel, M. Grégoire, D. Jean, C. Blanquart
• Journal: Molecular Cancer
• Published: 2018;17(1):148
• Type of article: Letter
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.

In plain English

This letter to the editor reported laboratory and patient-sample research on brain-derived neurotrophic factor (BDNF), a protein the authors proposed as a marker for malignant pleural mesothelioma (MPM). The article does not report an analysis of asbestos exposure. BDNF gene activity was higher in 179 MPM tumor samples than in 26 normal pleura samples (p = 0.0006). In pleural fluid, median BDNF was 95.26 pg/ml in MPM patients, 28.08 pg/ml in other cancers and 8.87 pg/ml in benign effusions. As a test separating MPM from all other effusions, BDNF had an area under the curve of 0.6972, with best specificity about 86.05% and sensitivity about 49.51%. MPM patients with pleural-fluid BDNF above the median survived 8.3 months, against 13 months for the others (p = 0.0061). In a public cancer database, survival was 12.4 months with high BDNF and 27.5 months with low BDNF. BDNF did not change mesothelioma cell growth. An antibody blocking BDNF cut fluid-induced blood-vessel cell growth by about 31%. The authors concluded BDNF is a new MPM biomarker and possible treatment target.

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: Letter to the editor reporting a laboratory study of tumor samples, pleural fluid samples, a public cancer gene database (TCGA) and cell experiments
• Who was studied: 179 frozen MPM tumor samples and 26 normal pleura samples; MPM and lung cancer cases from the TCGA database; a collection of pleural effusions from patients with MPM, other cancers or benign effusions (numbers not given in the main text); 14 MPM pleural effusions in the blood-vessel cell experiments. Patients were recruited in France.
• Exposure: The article does not report an analysis of asbestos exposure; patient characteristics are in supplementary files not included in the text. The study measured levels of the protein BDNF, both its gene activity in tumors and its concentration in pleural fluid.
• Main results:
  • BDNF gene activity was significantly higher in MPM tumors than in normal pleura (p = 0.0006).
  • In the frozen tumor collection, patients with high BDNF had lower survival than patients with low BDNF: 15.9 versus 21.1 months (p = 0.0736). The difference was statistically significant at 3 years (p = 0.0401).
  • In the TCGA database, high BDNF was associated with lower survival than low BDNF: 12.4 versus 27.5 months (p < 0.0001).
  • In the TCGA cohort, MPM had the highest BDNF expression among 37 tumor types.
  • Median pleural fluid BDNF was 95.26 pg/ml in MPM samples, compared with 28.08 pg/ml in other neoplasia and 8.87 pg/ml in benign effusions.
  • Area under the curve for BDNF was 0.6710 (plus or minus 0.04) for separating MPM from other cancers, and 0.6972 (plus or minus 0.038) for separating MPM from all pleural effusions.
  • The best specificity of BDNF was about 86.05% and the best sensitivity about 49.51%.
  • MPM patients with pleural fluid BDNF above the median survived 8.3 months, compared with 13 months for the others (p = 0.0061).
  • BDNF had no effect on MPM cell growth or on the cells' sensitivity to cisplatin.
  • An anti-BDNF blocking antibody reduced the growth of umbilical vein endothelial (blood-vessel) cells induced by MPM pleural fluid by about 31%. Of 14 fluids, 11 were sensitive to the antibody and 3 were resistant.
• The authors' conclusion: The authors concluded that BDNF is a new interesting MPM biomarker and, because of its involvement in angiogenesis (blood-vessel formation), could be a new potential therapeutic target.
• Limitations the authors state:
  • The authors noted that the diagnostic value of BDNF seemed slightly lower than that of SMRP, another mesothelioma marker.
  • The authors stated that some pleural fluids resisted the blocking antibody, showing that BDNF is not the only factor driving fluid-induced angiogenesis.

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: Biomarker, Pleural Mesothelioma, Angiogenesis, Asbestos Exposure, Discovery, Pleural Effusion.

Related studies

• VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours — Y. Ohta, V. Shridhar, et al. (1999)
• Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma — J.G. Edwards, D.E. Swinson, et al. (2003)
• Impact of tumor angiogenesis in peritoneal mesothelioma after radical cytoreduction and hyperthermic intraperitoneal chemotherapy — T.C. Chua, P. Yao, et al. (2010)
• Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma — A. Scherpereel, B. Grigoriu, et al. (2006)
• The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease — K.J. O'Byrne, A.G. Dalgleish, et al. (2000)
• Induction of angiogenesis by intraperitoneal injection of asbestos fibers — R.M. Branchaud, J.L. MacDonald, et al. (1989)

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