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Alterations in cellular metabolism under different grades of glioma staging identified based on a multi-omics analysis strategy.

ABSTRACT: Glioma is a type of brain tumor closely related to abnormal cell metabolism. Firstly, multiple combinatorial sequencing studies have revealed this relationship. Genomic studies have identified gene mutations and gene expression disorders related to the development of gliomas, which affect cell metabolic pathways. In addition, transcriptome studies have revealed the genes and regulatory networks that regulate cell metabolism in glioma tissues. Metabonomics studies have shown that the metabolic pathway of glioma cells has changed, indicating their distinct energy and nutritional requirements. This paper focuses on the retrospective analysis of multiple groups combined with sequencing to analyze the changes in various metabolites during metabolism in patients with glioma. Finally, the changes in genes, regulatory networks, and metabolic pathways regulating cell metabolism in patients with glioma under different metabolic conditions were discussed. It is also proposed that multi-group metabolic analysis is expected to better understand the mechanism of abnormal metabolism of gliomas and provide more personalized methods and guidance for early diagnosis, treatment, and prognosis evaluation of gliomas.

SUBMITTER: Yan X

PROVIDER: S-EPMC10726964 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Alterations in cellular metabolism under different grades of glioma staging identified based on a multi-omics analysis strategy.

Yan Xianlei X Li Jinwei J Zhang Yang Y Liang Cong C Liang Pengcheng P Li Tao T Liu Quan Q Hui Xuhui X

Frontiers in endocrinology 20231204

Glioma is a type of brain tumor closely related to abnormal cell metabolism. Firstly, multiple combinatorial sequencing studies have revealed this relationship. Genomic studies have identified gene mutations and gene expression disorders related to the development of gliomas, which affect cell metabolic pathways. In addition, transcriptome studies have revealed the genes and regulatory networks that regulate cell metabolism in glioma tissues. Metabonomics studies have shown that the metabolic pa ...[more]

PMID: 38111705

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Project description:BackgroundThe incidence of glioma, a prevalent brain malignancy, is increasing, particularly among the elderly population. This study aimed to elucidate the clinical importance of epithelial-mesenchymal transition (EMT) in gliomas and its association with malignancy and prognosis.BackgroundThe incidence of glioma, particularly among elderly individuals, is on the rise. The malignancy of glioma is determined not only by the oncogenic properties of tumor cells but also by the composition of the tumor microenvironment, which includes immune system macrophages. The prevalence of M2-type macrophages typically fosters tumor progression, yet the underlying mechanism remains elusive. Our study explored the clinical importance of epithelial-mesenchymal transition (EMT) in gliomas and its association with malignancy and prognosis.MethodsOur study used the gene set variation analysis (GSVA) algorithm to classify different levels of EMT activation based on the transcriptomic and multi-omics data. Machine learning (ML) and single-cell analysis were integrated into our model for comprehensive analysis. A predictive model was constructed and in vitro experiments were performed to validate our findings.ResultsOur study classified 1,641 samples into two clusters based on EMT activation: the EMT-hot group and the EMT-cold group. The EMT-hot group had elevated copy number loss, tumor mutational burden (TMB), and a poorer survival rate. Conversely, the EMT-cold group showed a better survival rate, likely attributed to lower stromal and immune cell scores, as well as decreased expression of human leukocyte antigen-related genes. Driving genes were identified through weighted gene coexpression network analysis (WGCNA) and dimensionality reduction techniques. These genes were then utilized in the construction of a prognostic model using ML and protein-protein interaction (PPI) network analysis. Furthermore, the impact of the core genes identified through single-cell analysis on glioma prognosis was examined.ConclusionOur research underscores the efficacy of our model in predicting glioma prognosis and elucidates the connection between the M2 macrophages and EMT. Additionally, core genes such as LY96, C1QB, LGALS1, CSPG5, S100A8, and CHGB were identified as pivotal for mediating the occurrence of EMT induced by M2 macrophages.

Project description:BackgroundGlioma is the most common type of primary brain tumor in adults. Patients with the most malignant form have an overall survival time of <16 months. Although considerable progress has been made in defining the adapted therapeutic strategies, measures to counteract tumor escape have not kept pace, due to the developed resistance of malignant glioma. In fact, identifying the nature and role of distinct tumor-infiltrating immune cells in glioma patients would decipher potential mechanisms behind therapy failure.MethodsWe integrated into our study glioma transcriptomic datasets from the Cancer Genome Atlas (TCGA) cohort (154 GBM and 516 LGG patients). LM22 immune signature was built using CIBERSORT. Hierarchical clustering and UMAP dimensional reduction algorithms were applied to identify clusters among glioma patients either in an unsupervised or supervised way. Furthermore, differential gene expression (DGE) has been performed to unravel the top expressed genes among the identified clusters. Besides, we used the least absolute shrinkage and selection operator (LASSO) and Cox regression algorithm to set up the most valuable prognostic factor.ResultsOur study revealed, following gene enrichment analysis, the presence of two distinct groups of patients. The first group, defined as cluster 1, was characterized by the presence of immune cells known to exert efficient antitumoral immune response and was associated with better patient survival, whereas the second group, cluster 2, which exhibited a poor survival, was enriched with cells and molecules, known to set an immunosuppressive pro-tumoral microenvironment. Interestingly, we revealed that gene expression signatures were also consistent with each immune cluster function. A strong presence of activated NK cells was revealed in cluster 1. In contrast, potent immunosuppressive components such as regulatory T cells, neutrophils, and M0/M1/M2 macrophages were detected in cluster 2, where, in addition, inhibitory immune checkpoints, such as PD-1, CTLA-4, and TIM-3, were also significantly upregulated. Finally, Cox regression analysis further corroborated that tumor-infiltrating cells from cluster 2 exerted a significant impact on patient prognosis.ConclusionOur work brings to light the tight implication of immune components on glioma patient prognosis. This would contribute to potentially developing better immune-based therapeutic approaches.

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Alterations in cellular metabolism under different grades of glioma staging identified based on a multi-omics analysis strategy.

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Alterations in cellular metabolism under different grades of glioma staging identified based on a multi-omics analysis strategy.

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