Gene regulatory networks analysis for the discovery of prognostic genes in gliomas
Gliomas are the most common and aggressive primary tumors of the central nervous system. Dysregulated transcription factors (TFs) and genes have been implicated in glioma progression, yet these tumors' overall structure of gene regulatory networks (GRNs) remains undefined. We analyzed transcriptional data from 989 primary gliomas in The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) to address this. GRNs were reconstructed using the RTN package which identifies regulons-sets of genes regulated by a common TF based on co-expression and mutual information. Regulon activity was evaluated through Gene Set Enrichment Analysis. Elastic net regularization and Cox regression identified 31 and 32 prognostic genes in the TCGA and CGGA datasets, respectively, with 11 genes overlapping, many of which are associated with neural development and synaptic processes. GAS2L3, HOXD13, and OTP demonstrated the strongest correlations with survival outcomes among these. Single-cell RNA-seq analysis of 201,986 cells revealed distinct expression patterns for these genes in glioma subpopulations, particularly oligoprogenitor cells. This study uncovers key GRNs and prognostic genes in gliomas, offering new insights into tumor biology and potential therapeutic targets.
Authors
- Fernando Yuri Nery do Vale (ORCID: https://orcid.org/0000-0003-1763-343X)
- Mariana Boroni
- Otávio Cabral-Marques (ORCID: https://orcid.org/0000-0002-3183-6236)
- Rodrigo Juliani Siqueira Dalmolin (ORCID: https://orcid.org/0000-0002-1688-6155)
- Helder I. Nakaya (ORCID: https://orcid.org/0000-0001-5297-9108)
- Roseane Galdioli Nava (ORCID: https://orcid.org/0000-0001-7415-2136)
- Igor Salerno Filgueiras (ORCID: https://orcid.org/0000-0002-3493-4464)
- Dennyson Leandro M. Fonseca (ORCID: https://orcid.org/0000-0003-2567-5808)
- D. Alburquerque
- Pedro Marçal Barcelos (ORCID: https://orcid.org/0009-0006-1039-5984)
- Júlia Nakanishi Usuda (ORCID: https://orcid.org/0000-0002-1516-162X)
- Gustavo Cabral‐Miranda (ORCID: https://orcid.org/0000-0001-8351-4880)
- Lena F. Schimke (ORCID: https://orcid.org/0000-0002-5616-3410)
- Anny Silva Adri (ORCID: https://orcid.org/0009-0007-0275-6126)
- Ian Antunes Ferreira Bahia (ORCID: https://orcid.org/0000-0001-6950-6091)
- Yohan Lucas Gonçalves Corrêa
- Haroldo Dutra Dias
- Adriel Leal Nóbile
- Alexandre H. C. Marques
Institutions
- Universidade de São Paulo (BR)
- Hospital Israelita Albert Einstein (BR)
- Universidade Federal do Rio Grande do Norte (BR)
- Instituto Nacional de Câncer - INCA (BR)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-04-23
- DOI
- https://doi.org/10.1038/s41598-025-98542-7
- Citations
- 2
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.25
Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro