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能量代谢相关的 GLUD1 有助于 IDH 突变型脑胶质瘤的良好临床结局。

Energy metabolism-related GLUD1 contributes to favorable clinical outcomes of IDH-mutant glioma.

机构信息

Transplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, No.166 Daxuedong Road, Nanning, Guangxi, 530007, P.R. China.

Guangxi Key Laboratory of Organ Donation and Transplantation, Nanning, Guangxi, 530007, P.R. China.

出版信息

BMC Neurol. 2024 Sep 13;24(1):344. doi: 10.1186/s12883-024-03787-w.

Abstract

BACKGROUND

Glioma is the most common brain tumor. IDH mutations occur frequently in glioma, indicating a more favorable prognosis. We aimed to explore energy metabolism-related genes in glioma to promote the research and treatment.

METHODS

Datasets were obtained from TCGA and GEO databases. Candidate genes were screened by differential gene expression analysis, then functional enrichment analysis was conducted on the candidate genes. PPI was also carried out to help determine the target gene. GSEA and DO analysis were conducted in the different expression level groups of the target gene. Survival analysis and immune cell infiltrating analysis were performed as well.

RESULTS

We screened 34 candidate genes and selected GLUD1 as the target gene. All candidate genes were significantly enriched in 10 KEGG pathways and 330 GO terms. GLUD1 expression was higher in IDH-mutant samples than IDH-wildtype samples, and higher in normal samples than tumor samples. Low GLUD1 expression was related to poor prognosis according to survival analysis. Most types of immune cells were negatively related to GLUD1 expression, but monocytes and activated mast cells exhibited significantly positive correlation with GLUD1 expression. GLUD1 expression was significantly related to 119 drugs and 6 immune checkpoint genes. GLUD1 was able to serve as an independent prognostic indicator of IDH-mutant glioma.

CONCLUSION

In this study, we identified an energy metabolism-related gene GLUD1 potentially contributing to favorable clinical outcomes of IDH-mutant glioma. In glioma, GLUD1 related clinical outcomes and immune landscape were clearer, and more valuable information was provided for immunotherapy.

摘要

背景

脑胶质瘤是最常见的脑肿瘤。IDH 突变在脑胶质瘤中频繁发生,提示预后较好。我们旨在探索脑胶质瘤中与能量代谢相关的基因,以促进研究和治疗。

方法

从 TCGA 和 GEO 数据库中获取数据集。通过差异基因表达分析筛选候选基因,然后对候选基因进行功能富集分析。还进行了 PPI 以帮助确定靶基因。在靶基因的不同表达水平组中进行了 GSEA 和 DO 分析。进行了生存分析和免疫细胞浸润分析。

结果

我们筛选出 34 个候选基因,并选择 GLUD1 作为靶基因。所有候选基因在 10 个 KEGG 途径和 330 个 GO 术语中均显著富集。IDH 突变样本中的 GLUD1 表达高于 IDH 野生型样本,正常样本中的 GLUD1 表达高于肿瘤样本。根据生存分析,低 GLUD1 表达与预后不良相关。大多数类型的免疫细胞与 GLUD1 表达呈负相关,但单核细胞和活化的肥大细胞与 GLUD1 表达呈显著正相关。GLUD1 表达与 119 种药物和 6 种免疫检查点基因显著相关。GLUD1 可作为 IDH 突变型脑胶质瘤的独立预后指标。

结论

在这项研究中,我们确定了一个与能量代谢相关的基因 GLUD1,它可能有助于 IDH 突变型脑胶质瘤的良好临床结局。在脑胶质瘤中,GLUD1 相关的临床结局和免疫图谱更清晰,为免疫治疗提供了更有价值的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2c/11395857/9d5efaa927f1/12883_2024_3787_Fig1_HTML.jpg

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