ENTPD1 (CD39) and NT5E (CD73) expression in human glioblastoma: an in silico analysis.

IF 3 4区 医学 Q2 NEUROSCIENCES Purinergic Signalling Pub Date : 2024-06-01 Epub Date: 2023-07-04 DOI:10.1007/s11302-023-09951-0
Elizandra Braganhol, Guilherme Pamplona Bueno de Andrade, Guilherme Tomasi Santos, Marco Antônio Stefani
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Abstract

Glioblastoma (GB) is the most common primary brain tumor in adults and carries a dismal prognosis, despite the best available treatment. The 2021 WHO Classification of CNS tumors incorporated molecular profiling to better define the characteristics and prognosis of tumor types and subtypes. These recent advances in diagnosis have not yet resulted in breakthrough therapies capable of shifting the treatment paradigm. NT5E/CD73 is a cell surface enzyme that participates in a complex purinergic pathway in synergy with ENTPD1/CD39 producing extracellular adenosine (ADO) from ATP. ADO promotes tumor progression by inducing immunosuppression, stimulating adhesion, invasion, and angiogenesis. In this study, we performed an in silico analysis of 156 human glioblastoma samples in an unexplored public database to investigate the transcriptional levels of NT5E and ENTPD1. The analysis revealed a significant increase in transcription levels of the genes under study in GB samples versus non-tumor brain tissue samples, in concordance with previous studies. High transcriptional levels of NT5E or ENTPD1 were independently related to a decrease in overall survival (p = 5.4e-04; 1.1e-05), irrespective of the IDH mutation status. NT5E transcriptional levels were significantly higher in GB IDH wild-type patients compared to GB IDH-mutant; however, ENTPD1 levels showed no significant difference, p ≤ 0.001. This in silico study indicates the need for a deeper understanding of the purinergic pathway relation to GB development, also inspiring future population studies that could explore ENTPD1 and NT5E not only as prognostic markers but also as potential therapeutic targets.

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ENTPD1(CD39)和 NT5E(CD73)在人类胶质母细胞瘤中的表达:一项硅学分析。
胶质母细胞瘤(GB)是成人中最常见的原发性脑肿瘤,尽管有最好的治疗方法,但预后很差。2021 年世界卫生组织中枢神经系统肿瘤分类纳入了分子图谱分析,以更好地界定肿瘤类型和亚型的特征和预后。最近在诊断方面取得的这些进展尚未带来能够改变治疗模式的突破性疗法。NT5E/CD73 是一种细胞表面酶,与 ENTPD1/CD39 协同参与复杂的嘌呤能途径,从 ATP 生成细胞外腺苷 (ADO)。ADO 通过诱导免疫抑制、刺激粘附、侵袭和血管生成来促进肿瘤进展。在这项研究中,我们对未开发的公共数据库中的 156 个人类胶质母细胞瘤样本进行了硅分析,以研究 NT5E 和 ENTPD1 的转录水平。分析结果显示,与非肿瘤脑组织样本相比,GB样本中研究基因的转录水平明显升高,这与之前的研究结果一致。无论IDH突变状态如何,NT5E或ENTPD1的高转录水平都与总生存率的下降独立相关(p = 5.4e-04; 1.1e-05)。GB IDH野生型患者的NT5E转录水平明显高于GB IDH突变型患者;然而,ENTPD1水平没有明显差异,p ≤ 0.001。这项硅学研究表明,需要更深入地了解嘌呤能通路与 GB 发展的关系,这也启发了未来的人群研究,不仅可以将 ENTPD1 和 NT5E 作为预后标志物,还可以将其作为潜在的治疗靶点。
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来源期刊
Purinergic Signalling
Purinergic Signalling 医学-神经科学
CiteScore
6.60
自引率
17.10%
发文量
75
审稿时长
6-12 weeks
期刊介绍: Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.
期刊最新文献
Correction to: Preparation and preliminary evaluation of a tritium-labeled allosteric P2X4 receptor antagonist. Machine learning-aided search for ligands of P2Y6 and other P2Y receptors. Purinergic regulation of pulmonary vascular tone. Role of ecto-5'-nucleotidase in bladder function activity and smooth muscle contractility. Unexpected role of microglia and P2Y12 in the induction of and emergence from anesthesia.
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