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

IF 3 4区 医学 Q2 NEUROSCIENCES Purinergic Signalling Pub Date : 2024-07-08 DOI:10.1007/s11302-024-10035-w
Marco Antônio Stefani, Elizandra Braganhol, Guilherme Tomasi Santos, Samuel Masao Suwa, Daiane Dias Cabeleira, Guilherme Pamplona Bueno de Andrade
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Abstract

Medulloblastoma is the most common malignant tumor in the pediatric population. Its classification has incorporated key molecular variations alongside histological characterization. CD39 (also known as ENTPD1) and CD73 (also known as NT5E), enzymes of the purinergic signaling pathway, act in synergy to generate extracellular adenosine, creating an immunosuppressive tumor microenvironment. Our study examined the expression of mRNA of these genes in previously described transcriptome data sets of medulloblastoma patient samples from the Cavalli Cohort (n = 763). Survival distribution was estimated according to the Kaplan-Meier method using a median cut-off and log-rank statistics (p ≤ 0.05). In non-WNT and non-SHH medulloblastoma Group 4 (n = 264), the high expression of ENTPD1 and NT5E was significantly related to a lower overall survival (p = 2.7e-04; p = 2.6e-03). In the SHH-activated group (n = 172), the high expression of ENTPD1 was significantly related to lower overall survival (p = 7.8e-03), while the high expression of NT5E was significantly related to greater overall survival (p = 0.017). In the WNT group (n = 63), the expressions of ENTPD1 and NT5E were not significantly correlated with overall survival (p = 0.212; p = 0.101). In non-WNT and non-SHH medulloblastoma Group 3 (n = 113), the high expression of ENTPD1 was significantly related to greater survival (p = 0.034), while expression of NT5E was not significantly related to survival of patients (p = 0.124). This in silico analysis indicates that ENTPD1 (CD39) and NT5E (CD73) can be seen as potential prognostic markers and therapeutic targets for primary medulloblastomas in non-WNT and non-SHH Group 4.

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ENTPD1(CD39)和NT5E(CD73)在人髓母细胞瘤中的表达:硅分析。
髓母细胞瘤是儿科最常见的恶性肿瘤。在对其进行分类时,除了组织学特征外,还纳入了关键的分子变异。CD39(又称ENTPD1)和CD73(又称NT5E)是嘌呤能信号通路的酶,它们协同作用产生细胞外腺苷,形成免疫抑制性肿瘤微环境。我们的研究检测了先前描述的卡瓦利队列(Cavalli Cohort)髓母细胞瘤患者样本(n = 763)转录组数据集中这些基因的 mRNA 表达。根据 Kaplan-Meier 方法,使用中位数截断和对数秩统计(P ≤ 0.05)估算了生存率分布。在非WNT和非SHH髓母细胞瘤第4组(n = 264)中,ENTPD1和NT5E的高表达与较低的总生存率显著相关(p = 2.7e-04;p = 2.6e-03)。在SHH激活组(n = 172)中,ENTPD1的高表达与较低的总生存率显著相关(p = 7.8e-03),而NT5E的高表达与较高的总生存率显著相关(p = 0.017)。在WNT组(n = 63)中,ENTPD1和NT5E的表达与总生存率无明显相关性(p = 0.212; p = 0.101)。在非WNT和非SHH髓母细胞瘤第3组(n = 113)中,ENTPD1的高表达与患者的生存率明显相关(p = 0.034),而NT5E的表达与患者的生存率无明显关系(p = 0.124)。这项硅分析表明,ENTPD1(CD39)和NT5E(CD73)可被视为非WNT和非SHH第4组原发性髓母细胞瘤的潜在预后标志物和治疗靶点。
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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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