Caracterização da rede regulatória e descoberta de genes prognósticos cm gliomas

Author(s)

Pedro Marçal Barcelos

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2025-02-26

Examining board members

Otávio Cabral Marques; Paula Paccielli Freire Barguil; Rodrigo Juliani Siqueira Dalmolin; Rodrigo Nalio Ramos

• Advisor: Otávio Cabral Marques

Abstract

Gliomas, the most prevalent and aggressive primary tumors of the central nervous system, are charactcrized by dysregulatcd transcription factors (TFs) and aberrant gene expression. Dcspite these insights, the architecture of gene regulatory networks (GRNs) driving glioma progression remains poorly understood. Deciphering these networks is vital for identifying therapeutic vulnerabilities and improving patient outcomes. We analyzed transcriptomic data from 989 primary gliomas using The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). GRNs were reconstructed through the RTN package, and regulon activity was assessed using Gene Set Enrichment Analysis (GSEA). Elastic net regularization and Cox proportional hazards regression identified prognostic genes associated with survival. Our analysis revealed 31 and 32 prognostic genes in the TCGA and CGGA cohorts, respectively, with 11 genes shared between datasets. Functional enrichment showed that many of these genes are involved in neural development and synaptic processes. Among the top candidates, GAS2L3, HOXD13, and OTP were robustly associated with survival outcomes. Single-cell RNA-sequencing of 201 ,986 glioma cells identified distinct expression pattems for these genes, particularly within oligoprogenitor cell populations. This study provides a comprehensive map of GRNs in gliomas and identifies novel prognostic markers with potential clinicai significance. By elucidating key regulatory networks and their associated genes, we lay the groundwork for future investigations into glioma biology and the development of targeted therapeutic strategies. (AU)

• FAPESP's process: 23/06086-6 - SYSTEMIC INTEGRATIVE ANALYSIS OF TUMORS ASSOCIATED WITH HUMAN ONCOVIRUS INFECTIONS
• Grantee: Pedro Marçal Barcelos
• Support Opportunities: Scholarships in Brazil - Master