Activation of BDNF/TrkB/Akt pathway is associated with aggressiveness and unfavorable survival in oral squamous cell carcinoma

• Published in: Oral diseases Vol. 25; no. 8; pp. 1925 - 1936
• Main Authors: Moraes, Juliana Kern de, Wagner, Vivian Petersen, Fonseca, Felipe Paiva, Amaral‐Silva, Gleyson Kleber do, de Farias, Caroline Brunetto, Pilar, Emily Ferreira Salles, Gregianin, Lauro, Roesler, Rafael, Vargas, Pablo Agustin, Martins, Manoela Domingues
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.11.2019
• Subjects: AKT protein; biomarker; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell survival; Dentistry; Head & neck cancer; head and neck cancer; Humans; immunohistochemistry; Leukokeratosis; Medical prognosis; Mouth Neoplasms - mortality; Mouth Neoplasms - pathology; Mucosa; Oral cancer; Oral squamous cell carcinoma; predictive value; Predictive Value of Tests; prognosis; Protein-tyrosine kinase receptors; Proto-Oncogene Proteins c-akt; Receptor, trkB - genetics; Receptor, trkB - metabolism; Ribosomal protein S6; Senescence; Squamous cell carcinoma; TrkB receptors; predictive value; immunohistochemistry; head and neck cancer; biomarker; prognosis
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.13190

Objectives To evaluate the expression of brain‐derived neurotrophic factor (BDNF), its tyrosine kinase receptor B (TrkB), and two downstream targets of this pathway, Akt and ribosomal protein S6 (RPS6), in normal oral mucosa (NOM), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC) and correlate this expression with OSCC patients’ outcomes, cell senescence, and “stemness” profile. Materials and Methods Ten cases of NOM, 32 OL, and 72 primary OSCC were included. Immunohistochemical analysis for BDNF, TrkB, p‐TrkB, p‐Akt, and p‐RPS6 was performed. Cell senescence and stemness profile of OSCC were evaluated through p16 and BMI‐1 immunohistochemical expression, respectively. The slides were scanned into high‐resolution images and quantified through digital analysis. Results Oral squamous cell carcinoma presented increased expression of BDNF/TrkB/Akt pathway compared to NOM and OL. OSCC diagnosed in advanced clinical stages presented an upregulation of BDNF and p‐TrkB. BDNF and p‐Akt were identified as predictors of poor disease‐specific survival. The increase in stemness profile was correlated with a decrease in p‐TrkB and p‐Akt expression. Conclusions BDNF/TrkB/Akt pathway is significantly increased in malignant cells from OSCC. Moreover, BDNF and Akt represent biomarkers capable to predict a poor prognosis of OSCC patients.