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

Comput Biol Med

Human and Mammalian Genetics Group, Departamento de Fisiología, Genética y Microbiología, Facultad de Ciencias, Universidad de Alicante, Alicante, Spain; 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, 03203, Alicante, Spain; Unidad de Genética Molecular, Hospital General Universitario de Elche, Camí de l'Almazara 11, Elche, 03203, Alicante, Spain. Electronic address:

Published: September 2024

AI Article Synopsis

  • This study explores deregulated pathways and biological functions in human glioblastoma (GBM) by comparing gene expression in GBM patients to healthy brain tissue using a custom DNA microarray.
  • The analysis identified 16 key genes that were either up-regulated or down-regulated in GBM, which were validated through RT-qPCR and used to create protein-protein interaction networks.
  • The findings highlight the potential of these genes and their pathways as targets for innovative GBM therapies, suggesting that some compounds aimed at these genes are already in clinical use.

Article Abstract

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.

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http://dx.doi.org/10.1016/j.compbiomed.2024.108833DOI Listing

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