Identification of new targets for glioblastoma therapy based on a DNA expression microarray

被引：0
作者：
Larriba E. [1 ,7 ]
de Juan Romero C. [2 ,3 ]
García-Martínez A. [2 ,4 ,8 ]
Quintanar T. [5 ]
Rodríguez-Lescure Á. [2 ,5 ,6 ]
Soto J.L. [2 ,4 ]
Saceda M. [2 ,3 ]
Martín-Nieto J. [1 ]
Barberá V.M. [1 ,2 ,4 ]
机构：
[1] Human and Mammalian Genetics Group, Departamento de Fisiología, Genética y Microbiología, Facultad de Ciencias, Universidad de Alicante, Alicante
[2] Unidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l'Almazara 11, Elche, Alicante
[3] Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Avda, Universidad s/n, Ed. Torregaitán, Elche
[4] Unidad de Genética Molecular, Hospital General Universitario de Elche, Camí de l'Almazara 11, Elche, Alicante
[5] Servicio de Oncología Médica. Hospital General Universitario de Elche, Camí de l'Almazara 11, Elche, Alicante
[6] School of Medicine. Universidad Miguel Hernández de Elche. Investigator, Spanish Breast Cancer Research Group (GEICAM)
[7] Instituto de Bioingeniería, Universidad Miguel Hernández, Elche
来源：
Computers in Biology and Medicine | 2024年 / 179卷
关键词：
Cancer therapy; DNA microarray; Gene expression; Glioblastoma; Molecular interaction networks;
D O I：
10.1016/j.compbiomed.2024.108833
中图分类号：
学科分类号：
摘要：
This study provides a comprehensive perspective on the deregulated pathways and impaired biological functions prevalent in human glioblastoma (GBM). In order to characterize differences in gene expression between individuals diagnosed with GBM and healthy brain tissue, we have designed and manufactured a specific, custom DNA microarray. The results obtained from differential gene expression analysis were validated by RT-qPCR. The datasets obtained from the analysis of common differential expressed genes in our cohort of patients were used to generate protein-protein interaction networks of functionally enriched genes and their biological functions. This network analysis, let us to identify 16 genes that exhibited either up-regulation (CDK4, MYC, FOXM1, FN1, E2F7, HDAC1, TNC, LAMC1, EIF4EBP1 and ITGB3) or down-regulation (PRKACB, MEF2C, CAMK2B, MAPK3, MAP2K1 and PENK) in all GBM patients. Further investigation of these genes and enriched pathways uncovered in this investigation promises to serve as a foundational step in advancing our comprehension of the molecular mechanisms underpinning GBM pathogenesis. Consequently, the present work emphasizes the critical role that the unveiled molecular pathways likely play in shaping innovative therapeutic approaches for GBM management. We finally proposed in this study a list of compounds that target hub of GBM-related genes, some of which are already in clinical use, underscoring the potential of those genes as targets for GBM treatment. © 2024 The Authors
引用
收藏
相关论文
共 122 条
[1]  
Weller M., Et al., EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood, Nat. Rev. Clin. Oncol., 18, 3, pp. 170-186, (2021)
[2]  
Louis D.N., Et al., The 2021 WHO classification of tumors of the central nervous system: a summary, Neuro Oncol., 23, 8, pp. 1231-1251, (2021)
[3]  
Mair M.J., Et al., A basic review on systemic treatment options in WHO grade II-III gliomas, Cancer Treat Rev., 92, (2021)
[4]  
Hamid M., Et al., Chemotherapy toxicity in older adults optimized by geriatric assessment and intervention: a non-comparative analysis, Curr. Oncol., 29, 9, pp. 6167-6176, (2022)
[5]  
Carlsson S.K., Brothers S.P., Wahlestedt C., Emerging treatment strategies for glioblastoma multiforme, EMBO Mol. Med., 6, 11, pp. 1359-1370, (2014)
[6]  
Fatai A.A., Gamieldien J., A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer, BMC Cancer, 18, 1, (2018)
[7]  
Verhaak R.G., Et al., Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1, Cancer Cell, 17, 1, pp. 98-110, (2010)
[8]  
Reifenberger G., Et al., Advances in the molecular genetics of gliomas - implications for classification and therapy, Nat. Rev. Clin. Oncol., 14, 7, pp. 434-452, (2017)
[9]  
Wen P.Y., Packer R.J., The 2021 WHO classification of tumors of the central nervous system: clinical implications, Neuro Oncol., 23, 8, pp. 1215-1217, (2021)
[10]  
Montella L., Et al., Looking beyond the glioblastoma mask: is genomics the right path?, Front. Oncol., 12, (2022)
12345678910