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综合分析揭示了unc-5 神经纤毛蛋白受体A(UNC5A)在胶质瘤中的潜在预后作用和免疫价值。

Integrative analysis reveals the potential prognostic roles and immunological values of unc-5 netrin receptor A (UNC5A) in glioma.

作者信息

Qian Wenbo, Zhang Lei, Zhang Fenglin, Ye Jingliang, Wan Zhiping, Chen Huairui, Luo Chun

机构信息

Department of Neurosurgery, Tongji Hospital of Tongji University, School of Medicine, Tongji University, Putuo District, No. 389 Xincun Road, Shanghai, 200092, China.

出版信息

Discov Oncol. 2024 Jul 22;15(1):297. doi: 10.1007/s12672-024-01174-y.

DOI:10.1007/s12672-024-01174-y
PMID:39039366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11263319/
Abstract

BACKGROUND

UNC5A had been reported to play crucial roles in multiple cancers. However, little was known about the associations among UNC5A and glioma. Therefore, we first combined scRNA-seq, proteomics, as well as bulk RNA-seq in order to investigate UNC5A's functions in gliomas.

METHODS

Online databases provided scRNA-seq, proteomics, as well as bulk RNA-seq data on UNC5A in gliomas. The following procedures were conducted in order: QRT-PCR, Norman chart, gene set enrichment analysis (GSEA), and univariate/multifactor Cox regression analyses. We further explored the associations among UNC5A and tumor immunity.

RESULTS

By comparing gliomas with normal tissues, the TCGA dataset showed a significantly reduced expression of UNC5A, which was also confirmed by GSE50161, GSE4290, and QRT-PCR findings (p < 0.05). In both the TCGA and CGGA datasets, gliomas patients with low-UNC5A expression would have poorer overall survival (OS) prognoses (p < 0.05). ScRNA-seq analysis by the CancerSEA online website presented that UNC5A had a low expression in various glioma clusters and significantly associated with six functional states. Moreover, UNC5A might be a reliable independent biomarker of OS in gliomas patients (p < 0.05). Based on the results of GSEA, UNC5A might be connected to three significant pathways in gliomas. We also successfully created a Norman chart to assess the OS prognoses of these patients. Additionally, in aspects of tumor immunity, the infiltration levels of immune cells in LGG, the immune cell pathways, tumor immune microenvironment, as well as immune checkpoints in both LGG and GBM were revealed to be significantly influenced by UNC5A (p < 0.05).

CONCLUSIONS

UNC5A was found to have prognostic and immunological significance in gliomas, offering patients with gliomas new treatment options.

摘要

背景

据报道,UNC5A在多种癌症中发挥关键作用。然而,关于UNC5A与胶质瘤之间的关联却知之甚少。因此,我们首先结合单细胞RNA测序(scRNA-seq)、蛋白质组学以及批量RNA测序,以研究UNC5A在胶质瘤中的功能。

方法

在线数据库提供了关于胶质瘤中UNC5A的scRNA-seq、蛋白质组学以及批量RNA测序数据。按以下顺序进行操作:实时定量聚合酶链反应(QRT-PCR)、诺莫图、基因集富集分析(GSEA)以及单因素/多因素Cox回归分析。我们进一步探究了UNC5A与肿瘤免疫之间的关联。

结果

通过将胶质瘤与正常组织进行比较,肿瘤基因组图谱(TCGA)数据集显示UNC5A表达显著降低,这也得到了基因表达综合数据库(GSE)50161、GSE4290以及QRT-PCR结果的证实(p < 0.05)。在TCGA和中国胶质瘤基因组图谱(CGGA)数据集中,UNC5A低表达的胶质瘤患者总生存期(OS)预后较差(p < 0.05)。通过CancerSEA在线网站进行的scRNA-seq分析表明,UNC5A在各种胶质瘤簇中表达较低,且与六种功能状态显著相关。此外,UNC5A可能是胶质瘤患者OS的可靠独立生物标志物(p < 0.05)。基于GSEA结果,UNC5A可能与胶质瘤中的三条重要通路相关。我们还成功创建了诺莫图以评估这些患者的OS预后。此外,在肿瘤免疫方面,低级别胶质瘤(LGG)中免疫细胞的浸润水平、免疫细胞通路、肿瘤免疫微环境以及LGG和胶质母细胞瘤(GBM)中的免疫检查点均显示受UNC5A显著影响(p < 0.05)。

结论

发现UNC5A在胶质瘤中具有预后和免疫学意义,为胶质瘤患者提供了新的治疗选择。

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