Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/fonc.2021.668090 http://hdl.handle.net/11449/208741 |
Resumo: | Glioblastoma (GBM) is the most lethal and frequent type of brain tumor, leading patients to death in approximately 14 months after diagnosis. GBM treatment consists in surgical removal followed by radio and chemotherapy. However, tumors commonly relapse and the treatment promotes only a slight increase in patient survival. Thus, uncovering the cellular mechanisms involved in GBM resistance is of utmost interest, and the use of cell lines has been shown to be an extremely important tool. In this work, the exploration of RNAseq data from different GBM cell lines revealed different expression signatures, distinctly correlated with the behavior of GBM cell lines regarding proliferation indexes and radio-resistance. U87MG and U138MG cells, which presented expressively reduced proliferation and increased radio-resistance, showed a particular expression signature encompassing enrichment in many extracellular matrix (ECM) and receptor genes. Contrasting, U251MG and T98G cells, that presented higher proliferation and sensibility to radiation, exhibited distinct signatures revealing consistent enrichments for DNA repair processes and although several genes from the ECM-receptor pathway showed up-regulation, enrichments for this pathway were not detected. The ECM-receptor is a master regulatory pathway that is known to impact several cellular processes including: survival, proliferation, migration, invasion, and DNA damage signaling and repair, corroborating the associations we found. Furthermore, searches to The Cancer Genome Atlas (TCGA) repository revealed prognostic correlations with glioma patients for the majority of genes highlighted in the signatures and led to the identification of 31 ECM-receptor genes individually correlated with radiation responsiveness. Interestingly, we observed an association between the number of upregulated genes and survivability greater than 5 years after diagnosis, where almost all the patients that presented 21 or more upregulated genes were deceased before 5 years. Altogether our findings suggest the clinical relevance of ECM-receptor genes signature found here for radiotherapy decision and as biomarkers of glioma prognosis. |
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Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing RadiationECM-receptorsexpression profilingextracellular matrixGBM cell linesglioblastomaradioresistanceGlioblastoma (GBM) is the most lethal and frequent type of brain tumor, leading patients to death in approximately 14 months after diagnosis. GBM treatment consists in surgical removal followed by radio and chemotherapy. However, tumors commonly relapse and the treatment promotes only a slight increase in patient survival. Thus, uncovering the cellular mechanisms involved in GBM resistance is of utmost interest, and the use of cell lines has been shown to be an extremely important tool. In this work, the exploration of RNAseq data from different GBM cell lines revealed different expression signatures, distinctly correlated with the behavior of GBM cell lines regarding proliferation indexes and radio-resistance. U87MG and U138MG cells, which presented expressively reduced proliferation and increased radio-resistance, showed a particular expression signature encompassing enrichment in many extracellular matrix (ECM) and receptor genes. Contrasting, U251MG and T98G cells, that presented higher proliferation and sensibility to radiation, exhibited distinct signatures revealing consistent enrichments for DNA repair processes and although several genes from the ECM-receptor pathway showed up-regulation, enrichments for this pathway were not detected. The ECM-receptor is a master regulatory pathway that is known to impact several cellular processes including: survival, proliferation, migration, invasion, and DNA damage signaling and repair, corroborating the associations we found. Furthermore, searches to The Cancer Genome Atlas (TCGA) repository revealed prognostic correlations with glioma patients for the majority of genes highlighted in the signatures and led to the identification of 31 ECM-receptor genes individually correlated with radiation responsiveness. Interestingly, we observed an association between the number of upregulated genes and survivability greater than 5 years after diagnosis, where almost all the patients that presented 21 or more upregulated genes were deceased before 5 years. Altogether our findings suggest the clinical relevance of ECM-receptor genes signature found here for radiotherapy decision and as biomarkers of glioma prognosis.Universidade Estadual PaulistaSchool of Pharmaceutical Sciences São Paulo State University (UNESP)Center for Cell-Based Therapy (CTC) Regional Blood Center of Ribeirão PretoDepartment of Genetics Ribeirão Preto Medical School University of São Paulo (USP)Radiation Oncology Branch National Cancer Institute National Institutes of Health (NIH)School of Pharmaceutical Sciences São Paulo State University (UNESP)Universidade Estadual Paulista (Unesp)Regional Blood Center of Ribeirão PretoUniversidade de São Paulo (USP)National Institutes of Health (NIH)Serafim, Rodolfo Bortolozo [UNESP]da Silva, Patrick [UNESP]Cardoso, CibeleDi Cristofaro, Luis Fernando Macedo [UNESP]Netto, Renato Petitto [UNESP]de Almeida, Rodrigo [UNESP]Navegante, Geovana [UNESP]Storti, Camila Baldinde Sousa, Juliana Ferreirade Souza, Felipe CantoPanepucci, RodrigoMoreira, Cristiano Gallina [UNESP]Penna, Larissa Siqueira [UNESP]Silva, Wilson AraujoValente, Valeria [UNESP]2021-06-25T11:18:15Z2021-06-25T11:18:15Z2021-05-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fonc.2021.668090Frontiers in Oncology, v. 11.2234-943Xhttp://hdl.handle.net/11449/20874110.3389/fonc.2021.6680902-s2.0-85107370488Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Oncologyinfo:eu-repo/semantics/openAccess2021-10-23T19:02:27Zoai:repositorio.unesp.br:11449/208741Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T19:02:27Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation |
title |
Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation |
spellingShingle |
Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation Serafim, Rodolfo Bortolozo [UNESP] ECM-receptors expression profiling extracellular matrix GBM cell lines glioblastoma radioresistance |
title_short |
Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation |
title_full |
Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation |
title_fullStr |
Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation |
title_full_unstemmed |
Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation |
title_sort |
Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation |
author |
Serafim, Rodolfo Bortolozo [UNESP] |
author_facet |
Serafim, Rodolfo Bortolozo [UNESP] da Silva, Patrick [UNESP] Cardoso, Cibele Di Cristofaro, Luis Fernando Macedo [UNESP] Netto, Renato Petitto [UNESP] de Almeida, Rodrigo [UNESP] Navegante, Geovana [UNESP] Storti, Camila Baldin de Sousa, Juliana Ferreira de Souza, Felipe Canto Panepucci, Rodrigo Moreira, Cristiano Gallina [UNESP] Penna, Larissa Siqueira [UNESP] Silva, Wilson Araujo Valente, Valeria [UNESP] |
author_role |
author |
author2 |
da Silva, Patrick [UNESP] Cardoso, Cibele Di Cristofaro, Luis Fernando Macedo [UNESP] Netto, Renato Petitto [UNESP] de Almeida, Rodrigo [UNESP] Navegante, Geovana [UNESP] Storti, Camila Baldin de Sousa, Juliana Ferreira de Souza, Felipe Canto Panepucci, Rodrigo Moreira, Cristiano Gallina [UNESP] Penna, Larissa Siqueira [UNESP] Silva, Wilson Araujo Valente, Valeria [UNESP] |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Regional Blood Center of Ribeirão Preto Universidade de São Paulo (USP) National Institutes of Health (NIH) |
dc.contributor.author.fl_str_mv |
Serafim, Rodolfo Bortolozo [UNESP] da Silva, Patrick [UNESP] Cardoso, Cibele Di Cristofaro, Luis Fernando Macedo [UNESP] Netto, Renato Petitto [UNESP] de Almeida, Rodrigo [UNESP] Navegante, Geovana [UNESP] Storti, Camila Baldin de Sousa, Juliana Ferreira de Souza, Felipe Canto Panepucci, Rodrigo Moreira, Cristiano Gallina [UNESP] Penna, Larissa Siqueira [UNESP] Silva, Wilson Araujo Valente, Valeria [UNESP] |
dc.subject.por.fl_str_mv |
ECM-receptors expression profiling extracellular matrix GBM cell lines glioblastoma radioresistance |
topic |
ECM-receptors expression profiling extracellular matrix GBM cell lines glioblastoma radioresistance |
description |
Glioblastoma (GBM) is the most lethal and frequent type of brain tumor, leading patients to death in approximately 14 months after diagnosis. GBM treatment consists in surgical removal followed by radio and chemotherapy. However, tumors commonly relapse and the treatment promotes only a slight increase in patient survival. Thus, uncovering the cellular mechanisms involved in GBM resistance is of utmost interest, and the use of cell lines has been shown to be an extremely important tool. In this work, the exploration of RNAseq data from different GBM cell lines revealed different expression signatures, distinctly correlated with the behavior of GBM cell lines regarding proliferation indexes and radio-resistance. U87MG and U138MG cells, which presented expressively reduced proliferation and increased radio-resistance, showed a particular expression signature encompassing enrichment in many extracellular matrix (ECM) and receptor genes. Contrasting, U251MG and T98G cells, that presented higher proliferation and sensibility to radiation, exhibited distinct signatures revealing consistent enrichments for DNA repair processes and although several genes from the ECM-receptor pathway showed up-regulation, enrichments for this pathway were not detected. The ECM-receptor is a master regulatory pathway that is known to impact several cellular processes including: survival, proliferation, migration, invasion, and DNA damage signaling and repair, corroborating the associations we found. Furthermore, searches to The Cancer Genome Atlas (TCGA) repository revealed prognostic correlations with glioma patients for the majority of genes highlighted in the signatures and led to the identification of 31 ECM-receptor genes individually correlated with radiation responsiveness. Interestingly, we observed an association between the number of upregulated genes and survivability greater than 5 years after diagnosis, where almost all the patients that presented 21 or more upregulated genes were deceased before 5 years. Altogether our findings suggest the clinical relevance of ECM-receptor genes signature found here for radiotherapy decision and as biomarkers of glioma prognosis. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T11:18:15Z 2021-06-25T11:18:15Z 2021-05-25 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fonc.2021.668090 Frontiers in Oncology, v. 11. 2234-943X http://hdl.handle.net/11449/208741 10.3389/fonc.2021.668090 2-s2.0-85107370488 |
url |
http://dx.doi.org/10.3389/fonc.2021.668090 http://hdl.handle.net/11449/208741 |
identifier_str_mv |
Frontiers in Oncology, v. 11. 2234-943X 10.3389/fonc.2021.668090 2-s2.0-85107370488 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers in Oncology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965289020915712 |