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

Patrick Smeele (1) , Sènan D’almeida (1, 2, 3) , Clément Meiller (4, 5, 6, 7) , Anne-Laure Chéné (1, 8) , Charly Liddell (1, 9) , Laurent Cellerin (1) , François Montagne (4, 5, 7, 6, 10, 11) , Sophie Deshayes (1) , Sarah Benziane (12, 13, 14) , Marie-Christine Copin (15) , Paul Hofman (16) , Françoise Le Pimpec-Barthes (4, 5, 6, 7, 17) , Henri Porte (18) , Arnaud Scherpereel (12, 14, 13) , Marc Grégoire (1) , Didier Jean (4, 5, 6, 7) , Christophe Blanquart (1)

1 CRCINA-ÉQUIPE 4 - Immunogenic Cell Death and Mesothelioma Therapy
2 Massachusetts General Hospital [Boston]
3 HMS - Harvard Medical School [Boston]
4 U1162 - Génomique Fonctionnelle des Tumeurs Solides
5 UPD5 - Université Paris Descartes - Paris 5
6 UPD7 - Université Paris Diderot - Paris 7
7 UP13 - Université Paris 13
8 Service d'Oncologie Médicale Thoracique et Digestive [CHU Nantes]
9 Service d’Anatomie et Cytologie Pathologiques [CHU Nantes]
10 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
11 Hôpital Albert Calmette
12 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
13 MESOCLIN - French National Network of Clinical Expert Centers for Malignant Pleural Mesothelioma Management
14 Pulmonary and Thoracic Oncology
15 Institut de Pathologie et Tumorothèque du C2RC
16 Laboratoire de Pathologie Clinique et Expérimentale
17 HEGP - Hôpital Européen Georges Pompidou [APHP]
18 Service de Chirurgie Thoracique [CHRU Lille]

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.

Keywords: Angiogenesis; Mesothelioma; BDNF; Biomarkers; Pleural effusions

Domains: Cancer

Patrick Smeele, Sènan D’almeida, Clément Meiller, Anne-Laure Chéné, Charly Liddell, et al.. Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis. Molecular Cancer, 2018, 17 (1), pp.148. ⟨10.1186/s12943-018-0891-0⟩. ⟨inserm-01904612⟩