Commentary on Hamilton et al. (2019): Why aren't cannabis use rates declining among US adolescents?
Commentary on Hamilton et al. (2019): Why aren't cannabis use rates declining among US adolescents?
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汉密尔顿等人的评论。
DOI：
10.1111/add.14758
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Borodovsky,JacobT
中科院分区：
文献类型：
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作者：
Grucza,RichardA;Borodovsky,JacobT
近年来，粘附G蛋白偶联受体（aGPCR）在癌症中的作用变得越来越明显。然而，支持该基因家族对血液恶性肿瘤，特别是急性髓性白血病（AML）的贡献的数据有限。在这里，我们使用公开的基因组数据来表征AML患者中33个aGPCR的表达，并检查这些基因的上调是否与患者的临床和分子特征相关。八种aGPCR基因（ADGRB 1、ADGR C2、ADGRD 1、ADGRE 1、ADGRE 2、ADGRE 5、ADGRG 1和/或ADGRG 3）中的一种或多种的上调与较短的总生存期（OS）显著相关（中位OS：11.8 vs 55.4个月;P< 0.0001）。在校正年龄、分子风险状态和移植状态后，这在多变量生存分析中也是显著的（风险比：1.73; 95%置信区间1.11-2.69;P= 0.015）。八种aGPCR的高表达与年龄较大显著相关（≥60;P= 0.011）。与aGPCR低表达的患者相比，aGPCR高表达的患者更频繁地被归类为低分子风险状态组，而良好风险状态组较少（分别为31%vs 17%P= 0.049和14%vs 28%P= 0.027）。通过免疫途径分析，我们在高aGPCR表达的患者中鉴定了最活化的途径中的白细胞介素-8信号通路。总体而言，我们的数据表明，特定的aGPCR在AML中经常上调，并与不良的临床结果相关。需要进一步的功能和机制分析来解决aGPCR在AML中的作用。
The role of adhesion G protein-coupled receptors (aGPCRs) in cancer has become increasingly evident in recent years. Yet, data supporting the contribution of this family of genes to hematological malignancies, particularly acute myeloid leukemia (AML) are limited. Here, we use publicly available genomic data to characterize the expression of the 33 aGPCRs in patients with AML and examine whether upregulation of these genes is associated with the clinical and molecular characteristics of patients. Upregulation in one or more of eight aGPCR genes (ADGRB1, ADGRC2, ADGRD1, ADGRE1, ADGRE2, ADGRE5, ADGRG1, and/orADGRG3) was significantly associated with shorter overall survival (OS) (median OS: 11.8 vs 55.4 months;P< 0.0001). This was also significant in multivariate survival analysis (hazard ratio: 1.73; 95% confidence interval 1.11–2.69;P= 0.015) after adjusting for age, molecular risk status, and transplant status. High expression of the eight aGPCRs was significantly associated with older age (≥60;P= 0.011). Patients with high aGPCRs expression were more frequently classified in the poor molecular risk status group and less in the good risk status group compared with patients with low aGPCRs expression (31% vs 17%P= 0.049 and 14% vs 28%P= 0.027, respectively). Via Ingenuity Pathway Analysis, we identified the interleukin-8 signaling pathway among the most activated pathways in patients with high aGPCRs expression. Overall, our data suggest that particular aGPCRs are frequently upregulated in AML and associated with poor clinical outcome. Future functional and mechanistic analyses are needed to address the role of aGPCRs in AML.