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鉴定与胶质瘤中维甲酸代谢相关的预后生物标志物,并分析它们对免疫微环境的影响。

Identification of prognostic biomarkers related to retinoic acid metabolism in gliomas and analysis of their impact on the immune microenvironment.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Xi'an, Jiaotong University, Xi'an, China.

Department of Radiotherapy, The Second Affiliated Hospital of Xi'an, Jiaotong University, Xi'an, China.

出版信息

Medicine (Baltimore). 2024 Oct 11;103(41):e39836. doi: 10.1097/MD.0000000000039836.

Abstract

Glioma is a primary tumor of the central nervous system. Numerous investigations have demonstrated that retinoic acid (RA) signaling plays an important role in glioblastoma. This research aimed to develop a RA metabolism-related gene signature associated with glioma. The RA metabolism-related differentially expressed genes were obtained through differential analysis of RA metabolism-related genes in GSE4290. The univariate Cox and least absolute shrinkage and selection operator regression analysis were adopted to build a RA metabolism-related glioma prognostic signature. We further conducted immune feature estimation and functional enrichment analysis between 2 risk subgroups. Finally, the potential drug-targeting prognostic genes were predicted through the DrugBank database. A sum of 10 RA metabolism-related differentially expressed genes between normal and tumor groups were identified. Then, a RA metabolism-related prognostic signature was built based on the 7 prognostic genes (ADH4, DHRS3, DHRS9, LRAT, RDH10, RDH12, and RDH5). Glioma patients were separated into 2 risk subgroups (low-risk vs high-risk) based on the median value of the risk score. We found that monocytes were negatively correlated with DHRS9, while activated naive CD4+T cell was positively correlated with RDH10. These prognostic genes participated in some immune-related processes, such as "B cell-mediated immunity." Finally, 4 drugs targeting DHRS3, LRAT, and RDH12 were predicted, including vitamin A, nicotinamide adenine dinucleotide, ethanol, and cyclohexylformamide. The prognostic signature comprised of ADH4, DHRS3, DHRS9, LRAT, RDH10, RDH12, and RDH5 based on RA metabolism was established, which provided a theoretical basis and reference value for the research of glioma.

摘要

神经胶质瘤是一种中枢神经系统的原发性肿瘤。大量研究表明,维甲酸(RA)信号在胶质母细胞瘤中起着重要作用。本研究旨在开发与神经胶质瘤相关的 RA 代谢相关基因特征。通过对 GSE4290 中 RA 代谢相关基因的差异分析,获得 RA 代谢相关差异表达基因。采用单变量 Cox 和最小绝对收缩和选择算子回归分析构建 RA 代谢相关神经胶质瘤预后特征。我们进一步在 2 个风险亚组之间进行免疫特征估计和功能富集分析。最后,通过 DrugBank 数据库预测潜在的药物靶向预后基因。在正常组和肿瘤组之间确定了 10 个 RA 代谢相关差异表达基因。然后,基于 7 个预后基因(ADH4、DHRS3、DHRS9、LRAT、RDH10、RDH12 和 RDH5)构建了 RA 代谢相关预后特征。根据风险评分的中位数,将神经胶质瘤患者分为 2 个风险亚组(低风险与高风险)。我们发现,DHRS9 与单核细胞呈负相关,而 RDH10 与激活的幼稚 CD4+T 细胞呈正相关。这些预后基因参与了一些免疫相关过程,如“B 细胞介导的免疫”。最后,预测了 4 种靶向 DHRS3、LRAT 和 RDH12 的药物,包括维生素 A、烟酰胺腺嘌呤二核苷酸、乙醇和环己基甲酰胺。基于 RA 代谢建立了由 ADH4、DHRS3、DHRS9、LRAT、RDH10、RDH12 和 RDH5 组成的预后特征,为神经胶质瘤的研究提供了理论基础和参考价值。

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