Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/25652
Title: Expression signatures of DNA repair genes correlate with survival prognosis of astrocytoma patients
Authors: Sousa, Juliana Ferreira de
Torrieri, Raul
Serafim, Rodolfo Bortolozo
Di Cristofaro, Luis Fernando Macedo
Escanfella, Fábio Dalbon
Ribeiro, Rodrigo
Zanette, Dalila Lucíola
Larson, Maria Luisa Paçó
Silva, Wilson Araujo da
Tirapelli, Daniela Pretti da Cunha
Neder, Luciano
Carlotti, Carlos Gilberto
Valente, Valeria
Affilliation: University of São Paulo State. Faculty of Pharmaceutical Sciences of Araraquara. Department of Clinical Analysis. Araraquara, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Cellular and Molecular Biology. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Center for Medical Genomics of the Clinical Hospital. Ribeirão Preto, SP, Brazil
University of São Paulo State. Faculty of Pharmaceutical Sciences of Araraquara. Department of Clinical Analysis. Araraquara, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Cellular and Molecular Biology. Ribeirão Preto, SP, Brazil
University of São Paulo State. Faculty of Pharmaceutical Sciences of Araraquara. Department of Clinical Analysis. Araraquara, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Cellular and Molecular Biology. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Cellular and Molecular Biology. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Cellular and Molecular Biology. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Genetics. Ribeirão Preto, SP, Brazil / Regional Blood Center of Ribeirão Preto. Center for Cell-Based Therapy. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Cellular and Molecular Biology. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Genetics. Ribeirão Preto, SP, Brazil / Regional Blood Center of Ribeirão Preto. Center for Cell-Based Therapy. Ribeirão Preto, SP, Brazil / National Institute of Science and Technology in Stem cell and Cell Therapy. Ribeirão Preto, SP, Brazil / University of São Paulo. Center for Integrative Systems Biology. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Surgery and Anatomy. Ribeirão Preto, SP, Brazil
University of São Paulo. Ribeirão Preto Medical School. Department of Pathology. Ribeirão Preto, SP, Brazil
University of São Paulo. Center for Integrative Systems Biology. Ribeirão Preto, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Pathology. Ribeirão Preto, SP, Brazil
University of São Paulo State. Faculty of Pharmaceutical Sciences of Araraquara. Department of Clinical Analysis. Araraquara, SP, Brazil / University of São Paulo. Ribeirão Preto Medical School. Department of Cellular and Molecular Biology. Ribeirão Preto, SP, Brazil / University of São Paulo. Center for Integrative Systems Biology. Ribeirão Preto, SP, Brazil
Abstract: Astrocytomas are the most common primary brain tumors. They are very resistant to therapies and usually progress rapidly to high-grade lesions. Here, we investigated the potential role of DNA repair genes in astrocytoma progression and resistance. To this aim, we performed a polymerase chain reaction array-based analysis focused on DNA repair genes and searched for correlations between expression patters and survival prognoses. We found 19 genes significantly altered. Combining these genes in all possible arrangements, we found 421 expression signatures strongly associated with poor survival. Importantly, five genes (DDB2, EXO1, NEIL3, BRCA2, and BRIP1) were independently correlated with worse prognoses, revealing single-gene signatures. Moreover, silencing of EXO1, which is remarkably overexpressed, promoted faster restoration of double-strand breaks, while NEIL3 knockdown, also highly overexpressed, caused an increment in DNA damage and cell death after irradiation of glioblastoma cells. These results disclose the importance of DNA repair pathways for the maintenance of genomic stability of high-grade astrocytomas and suggest that EXO1 and NEIL3 overexpression confers more efficiency for double-strand break repair and resistance to reactive oxygen species, respectively. Thereby, we highlight these two genes as potentially related with tumor aggressiveness and promising candidates as novel therapeutic targets.
Keywords: DNA repair
Astrocytoma
Glioblastoma
Tumor progression
Genomic instability
keywords: Reparo de DNA
Astrocitoma
Glioblastoma
Progressão tumoral
Instabilidade genômica
Issue Date: 2017
Publisher: Springer Verlag
Citation: SOUSA, J. F. et al. Expression signatures of DNA repair genes correlate with survival prognosis of astrocytoma patients
Description: Zanette, Dalila Lucíola. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.
DOI: 10.1177/1010428317694552
ISSN: 1010-4283
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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