Juliana Kern de Moraes1, Vivian Petersen Wagner1, Felipe Paiva Fonseca2, Gleyson Kleber do Amaral-Silva1, Caroline Brunetto de Farias3,4, Emily Ferreira Salles Pilar5, Lauro Gregianin4,6, Rafael Roesler3,4,7, Pablo Agustin Vargas1, Manoela Domingues Martins1,5,8. 1. Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil. 2. Department of Oral Surgery and Pathology, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Brazil. 3. Cancer and Neurobiology Laboratory, Experimental Research Center, Porto Alegre Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 4. Children's Cancer Institute, Porto Alegre, Brazil. 5. Experimental Pathology Unit, Clinics Hospital of Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 6. Pediatric Oncology Service, Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 7. Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. 8. Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Abstract
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.
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.
Authors: Mohammad Malekan; Sasan Salehi Nezamabadi; Elham Samami; Mehdi Mohebalizadeh; Amene Saghazadeh; Nima Rezaei Journal: J Cancer Res Clin Oncol Date: 2022-09-29 Impact factor: 4.322
Authors: Vivian P Wagner; Manoela D Martins; Esra Amoura; Virgilio G Zanella; Rafael Roesler; Caroline B de Farias; Colin D Bingle; Pablo A Vargas; Lynne Bingle Journal: Biomedicines Date: 2020-11-24