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

Autor(es)

de Moraes, Juliana Kern ^[1] ; Wagner, Vivian Petersen ^[1] ; Fonseca, Felipe Paiva ^[2] ; do Amaral-Silva, Gleyson Kleber ^[1] ; de Farias, Caroline Brunetto ^{[3, 4]} ; Salles Pilar, Emily Ferreira ^[5] ; Gregianin, Auro ^{[4, 6]} ; Roesler, Rafael ^{[7, 3, 4]} ; Vargas, Pablo Agustin ^[1] ; Martins, Manoela Domingues ^{[1, 8, 5]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Oral Diag, Piracicaba - Brazil

^[2] Univ Fed Minas Gerais, Sch Dent, Dept Oral Surg & Pathol, Belo Horizonte, MG - Brazil

^[3] Univ Fed Rio Grande do Sul, Porto Alegre Clin Hosp, Expt Res Ctr, Canc & Neurobiol Lab, Porto Alegre, RS - Brazil

^[4] Childrens Canc Inst, Porto Alegre, RS - Brazil

^[5] Univ Fed Rio Grande do Sul, Clin Hosp Porto Alegre, Expt Pathol Unit, Porto Alegre, RS - Brazil

^[6] Univ Fed Rio Grande do Sul, Clin Hosp, Pediat Oncol Serv, Porto Alegre, RS - Brazil

^[7] Univ Fed Rio Grande do Sul, Inst Basic Hlth Sci, Dept Pharmacol, Porto Alegre, RS - Brazil

^[8] Univ Fed Rio Grande do Sul, Sch Dent, Dept Oral Pathol, Porto Alegre, RS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ORAL DISEASES; v. 25, n. 8, p. 1925-1936, NOV 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 16/21785-4 - Relação da via de sinalização BDNF/TRKB com a agressividade e perfil de células tronco tumorais de neoplasias malignas de glândula salivar
• Beneficiário: Vivian Petersen Wagner
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado