Evaluation of the expression and potential prognosis of the genes present in the chr9p22.1-p21.3 locus in gliomas

• Grant number: 17/09749-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2017
• End date: August 31, 2019
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Rui Manuel Vieira Reis
• Grantee: Paola Gyuliane Gonçalves
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Gliomas are malignant brain tumors and are the most frequent among the central nervous system tumors. The majority of gliomas are untreatable, and when treated with the standard protocol, the mean survival is of approximately 14 months. The irrelevant success in the treatment of these tumors is not only due to the low understanding of their molecular bases, but also due to the use of a standard treatment for all the different subtypes of gliomas. Thus, our research group described a frequently deleted region (chr9p22.1-p21.3) in gliomas, with potentially important genes in prognosis of this neoplasia. Therefore, the objective of the present project is to analyze the expression and the prognostic potential of the genes present in this region, and evaluate the effects of loss of expression and reexpression of these genes in glioma's cell lines. First, we will analyze in silico (n > 600 cases) the potential prognosis of all the 27 genes present in this region in TCGA datasets and select between 2 and 4 genes to analyze. In sequence, we will analyze the protein expression (immunohistochemistry) and mRNA (qRT-PCR) expression in cell lines and glioma cases from Barretos Cancer Hospital and partners (n = 250 cases). Based on the results, the genes will be silenced and reexpressed in cell lines, and functional alterations will be evaluated (proliferation, apoptosis, migration and cell invasion). Finally, we will evaluate the response of these manipulated lines to the treatment with tomozolomide. These results may propose novel therapeutical approaches to the treatment of patients with intrinsically presence of this deletion. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRUNHARA, BRUNO B.; BECKER, ALINE P.; NEDER, LUCIANO; GONCALVES, PAOLA G.; DE OLIVEIRA, CRISTIANE; CLARA, CARLOS A.; REIS, RUI M.; BIDINOTTO, LUCAS T.. Evaluation of the prognostic potential of EGFL7 in pilocytic astrocytomas. NEUROPATHOLOGY, NOV 2020. (16/23919-8, 12/19590-0, 17/09749-5, 16/21727-4)

DA COSTA, BRUNO HENRIQUE BRESSAN; BECKER, ALINE PAIXAO; NEDER, LUCIANO; GONCALVES, PAOLA GYULIANE; DE OLIVEIRA, CRISTIANE; POLVERINI, ALLAN DIAS; CLARA, CARLOS AFONSO; TEIXEIRA, GUSTAVO RAMOS; REIS, RUI MANUEL; BIDINOTTO, LUCAS TADEU. EGFL7 expression profile in IDH-wildtype glioblastomas is associated with poor patient outcome. JOURNAL OF PATHOLOGY AND TRANSLATIONAL MEDICINE, v. N/A, p. 10-pg., 2022-06-15. (18/20737-1, 17/09749-5, 16/21727-4)

GONCALVES, PAOLA G.; REIS, RUI M.; BIDINOTTO, LUCAS T.. Significance of Chr9p22.1-p21.3 Deletion in Cancer Development: A Pan-cancer In Silico Analysis. ANTICANCER RESEARCH, v. 42, n. 11, p. 14-pg., 2022-11-01. (17/09749-5, 16/21727-4)

BRUNHARA, BRUNO B.; BECKER, ALINE P.; NEDER, LUCIANO; GONCALVES, PAOLA G.; DE OLIVEIRA, CRISTIANE; CLARA, CARLOS A.; REIS, RUI M.; BIDINOTTO, LUCAS T.. Evaluation of the prognostic potential of EGFL7 in pilocytic astrocytomas. NEUROPATHOLOGY, v. 41, n. 1, p. 8-pg., 2020-11-15. (16/21727-4, 16/23919-8, 17/09749-5, 12/19590-0)