Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation

Author(s):Show less -

Serafim, Rodolfo Bortolozo ^{[1, 2, 3]} ; da Silva, Patrick ^[2] ; Cardoso, Cibele ^{[1, 3]} ; Di Cristofaro, Luis Fernando Macedo ^[2] ; Netto, Renato Petitto ^[2] ; de Almeida, Rodrigo ^[2] ; Navegante, Geovana ^[2] ; Storti, Camila Baldin ^{[1, 3]} ; de Sousa, Juliana Ferreira ^[4] ; de Souza, Felipe Canto ^{[1, 3]} ; Panepucci, Rodrigo ^{[1, 3]} ; Moreira, Cristiano Gallina ^[2] ; Penna, Larissa Siqueira ^[2] ; Silva, Jr., Wilson Araujo ^{[1, 3]} ; Valente, Valeria ^{[1, 2, 3]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Araraquara, SP - Brazil

^[3] Reg Blood Ctr Ribeirao Preto, Ctr Cell Based Therapy CTC, Ribeirao Preto - Brazil

^[4] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 - USA

• Document type: Journal article
• Source: FRONTIERS IN ONCOLOGY; v. 11, MAY 25 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/05018-9 - Investigation of HJURP action (Holliday Junction Recognizing Protein) in DNA repair activity of glioblastoma cells
• Grantee: Valeria Valente
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/13465-1 - Functional characterization of HJURP (Holliday junction recognizing protein) in glioblastoma multiforme cells
• Grantee: Valeria Valente
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/24335-8 - Characterization of HJURP protein-protein interaction-networks in glioma cells submitted to different types of DNA damage
• Grantee: Rodrigo de Almeida
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/22799-4 - Characterization and strength prediction of promoters regulated by YgiV transcriptional factor of Salmonella enterica serovar Typhimurium
• Grantee: Patrick da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/12744-2 - Transcriptional YgiV role and VisP protein-protein interaction on chemical signaling and LPS assembly in Salmonella enterica sorovar Typhimurium pathogenesis
• Grantee: Patrick da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/15208-7 - Investigation of HJURP functions in the acquisition of stemness in glioblastoma lines
• Grantee: Rodrigo de Almeida
• Support Opportunities: Scholarships in Brazil - Doctorate