Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia
Acidic leucine-rich nuclear phosphoprotein-32A expression contributes to adverse outcome in acute myeloid leukemia
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DOI：
10.21037/atm.2020.02.54
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发表时间：
2020-03-01
影响因子：
--
通讯作者：
Feng, Cong
中科院分区：
文献类型：
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作者：
Huang, Sai;Huang, Zhi;Feng, Cong
背景资料：酸性富亮氨酸核磷蛋白-32A（ANP 32A）是一种新的组蛋白H3乙酰化调节剂，可促进急性髓性白血病（AML）的白血病发生。然而，其预后价值在AML.Methods：在这项研究中，我们评估了ANP 32A表达的预后意义，使用两个独立的大队列的细胞遗传学正常的AML（CN-AML）患者。对CN-AML组进行多因素分析。结果：ANP 32A过表达与CN-AML患者预后不良显著相关（OS：P=0.012，EFS：P=0.005，n=185; OS：P=0.041，n=232），以及欧洲白血病网络（ELN）中间I组（OS：P=0.018，EFS：P=0.045，n=115），国家综合癌症网络（NCCN）中度风险AML组非M3 AML组（OS：P = 0.034，EFS：P =0.011，n=435）。多因素分析进一步证实ANP 32A是CN-AML的高危因素。多组学分析显示ANP 32A的过度表达与癌基因和抑癌基因的异常表达、代谢和免疫相关通路的上调/下调、microRNA的失调以及CpG岛和第一外显子区域的低甲基化有关。
Background: Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) is a novel regulator of histone H3 acetylation and promotes leukemogenesis in acute myeloid leukemia (AML). However, its prognostic value in AML remains unclear.Methods: In this study, we evaluated the prognostic significance of ANP32A expression using two independent large cohorts of cytogenetically normal AML (CN-AML) patients. Multivariable analysis in CN-AML group was also presented. Based on the ANP32A expression, its related genes, dysregulation of pathways, interaction network analysis between microRNAs and target genes, as well as methylation analysis were performed to unveil the complex functions behind ANP32A.Results: Here we demonstrated overexpression of ANP32A was notably associated with unfavorable outcome in two independent cohorts of CN-AML patients (OS: P=0.012, EFS: P=0.005, n=185; OS: P=0.041, n=232), as well as in European Leukemia Net (ELN) Intermediate-I group (OS: P=0.018, EFS: P=0.045, n=115), National Comprehensive Cancer Network (NCCN) Intermediate Risk AML group (OS: P=0.048, EFS: P=0.039, n=225), and non-M3 AML group (OS: P=0.034, EFS: P=0.011, n=435). Multivariable analysis further validated ANP32A as a high-risk factor in CN-AML group. Multi-omics analysis presented overexpression of ANP32A was associated with aberrant expression of oncogenes and tumor suppressor, up/down-regulation of metabolic and immune-related pathways, dysregulation of microRNAs, and hypomethylation on CpG island and 1st Exon regions.Conclusions: We proved ANP32A as a novel, potential unfavorable prognosticator and therapeutic target for AML.