Full-Length TrkB Variant in NSCLC Is Associated with Brain Metastasis

• Published in: BioMed research international 2020, Vol.2020 (2020), p.1-7
• Main Authors: Cardaci, Vittorio, Innammorato, Marta, Vecchione, Andrea, Ricci, Alberto, Mancini, Rita, Raj, Enrico Rathina, Costarelli, Leopoldo, Giordano, Marco, Scozzi, Davide, Scarpino, Stefania, D'Ascanio, Michela, Lombardi, Mariangela, Cardillo, Giuseppe
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Antibodies; Biopsy; Brain; Brain cancer; Brain Neoplasms - genetics; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Care and treatment; Cell Adhesion; Cell Line, Tumor; Central nervous system; Female; Gene Expression Regulation, Neoplastic; Genetic aspects; Growth factors; Humans; Identification and classification; Immunohistochemistry; Kinases; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - genetics; Male; Metastases; Metastasis; Middle Aged; Mutation; Mutation - genetics; Nervous system; Non-small cell lung carcinoma; Patients; Phosphotransferases; Properties; Protein-tyrosine kinase; Receptor, trkB - genetics; Receptor, trkB - metabolism; Receptors; Small cell lung carcinoma; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Statistical methods; TrkB receptors; Tyrosine
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2020/4193541

Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their expression was related to preferential tumor entry into the central nervous system (CNS). By immunohistochemistry, 80% of the ADKs that metastasize to central nervous system expressed TrkB receptor compared to 33% expressing of ADKs without CNS metastasis. Moreover, ADKs with CNS metastasis showed an elevated expression of the full-length TrkB receptor. The TrkB receptor FL/T1 ratio was statistically higher in primary ADKs with brain metastasis compared to ADKs without brain metastasis. Our data indicate that TrkB full-length isoform expression in primary ADK cells may be associated with higher risk to develop brain metastasis. Therefore, TrkB receptor may possess prognostic and therapeutic implications in lung ADK.