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.
摘要:
髓母细胞瘤是儿科人群中最常见的恶性肿瘤。它的分类结合了关键的分子变异和组织学特征。CD39(也称为ENTPD1)和CD73(也称为NT5E),嘌呤能信号通路的酶,协同作用产生细胞外腺苷,创造免疫抑制肿瘤微环境.我们的研究检查了来自Cavalli队列(n=763)的髓母细胞瘤患者样品的先前描述的转录组数据集中这些基因的mRNA表达。根据Kaplan-Meier方法,使用中位数截止值和对数秩统计量(p≤0.05)估算生存分布。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期显著相关(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着相关(p=7.8e-03),而NT5E的高表达与更高的总生存率显着相关(p=0.017)。在WNT组(n=63)中,ENTPD1和NT5E的表达与总生存期无显著相关性(p=0.212;p=0.101).在非WNT和非SHH髓母细胞瘤组3(n=113)中,ENTPD1的高表达与更高的生存率显着相关(p=0.034),而NT5E的表达与患者的生存率没有显着相关(p=0.124)。这种计算机模拟分析表明,ENTPD1(CD39)和NT5E(CD73)可以被视为非WNT和非SHH组4中原发性髓母细胞瘤的潜在预后标志物和治疗靶标。