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Activation of BDNF/TrkB/Akt pathway is associated with aggressiveness and unfavorable survival in oral squamous cell carcinoma
Author(s) -
Moraes Juliana Kern de,
Wagner Vivian Petersen,
Fonseca Felipe Paiva,
AmaralSilva Gleyson Kleber do,
de Farias Caroline Brunetto,
Pilar Emily Ferreira Salles,
Gregianin Lauro,
Roesler Rafael,
Vargas Pablo Agustin,
Martins Manoela Domingues
Publication year - 2019
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.13190
Subject(s) - tropomyosin receptor kinase b , protein kinase b , immunohistochemistry , cancer research , brain derived neurotrophic factor , medicine , skp2 , pathology , neurotrophic factors , biology , signal transduction , receptor , microbiology and biotechnology , ubiquitin , ubiquitin ligase , biochemistry , gene
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.