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Assessing the metabolic status of glioma microenvironment using single cell transcriptomic data

Grant number: 22/16458-5
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2023
Effective date (End): August 31, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Tathiane Maistro Malta Pereira
Grantee:Felipe Pimenta Carcanholo
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Gliomas are brain tumors with low therapeutic response, heterogeneous and classified by histopathological characteristics and some molecular markers. In them, mutation in the gene isocitrate dehydrogenase 1 and 2 (IDH1/1DH2) can occur, which defines a different type of glioblastoma that has hypermethylation in the CpG islands, a phenotype known as G-CIMP, and it has a favorable prognosis when compared to with the unmutated. Differences between IDH-mutant and IDH-wild gliomas cannot be evidenced histologically, but they continue to be tumor types that are very different from each other, both in terms of molecular mode of action and potential drug targets. The reprogramming of energy metabolism is one of the hallmarks of cancer, as there is a high energy demand for tumor growth, requiring an adjustment in energy metabolism to serve as "fuel" for uncontrolled growth. Furthermore, it has already been seen that gene expression is heterogeneous, even in similar cell types. Thus, studies based solely on mass profiling may miss important information on cell-to-cell variability, and to avoid this loss a more accurate understanding of the transcriptome in individual cells is needed to understand its role in cellular functions. Thus, single-cell transcriptome (scRNA-seq) analysis can reveal rare and complex cell populations, uncover regulatory relationships between genes, and trace developmental trajectories of different cell lineages. Therefore, this project intends to compare the metabolic status of individual cells from the tumor microenvironment using RNA sequencing data from single cells, in mutant IDH and wild IDH gliomas. For this, scRNA-seq datasets from healthy cells and glioma tumor cells will be searched, a determination of metabolic signatures and, based on this signature, a standardization of the ssGSEA in order to create a metabolic score to compare the metabolic status of different populations of the tumor microenvironment. Based on understanding the metabolic status of tumor cells, it may be possible to understand the existing relationships between cells in intratumoral heterogeneity, which may help in the development of therapeutic targets.

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