基于生物信息学方法分析醛氧化酶1在急性淋巴细胞白血病患者中的表达及临床意义  

Analysis of the expression and clinical significance of Aldehyde Oxidase 1 in acute lymphoblastic leukemia based on bioinformatics methods

作　　者：李苗[1] 孔晓岩 王淑梅 LI Miao;KONG Xiao-yan;WANG Shu-mei(Department of Pediatrics,Capital Medical University,Beijing 100038,China;Department of Pharmacy,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Department of Pharmacy,Armedpolice Beijing Corps Hospital,Beijing 100027,China)

机构地区：[1]首都医科大学附属北京世纪坛医院儿科,北京100038 [2]首都医科大学附属北京世纪坛医院药学部,北京100038 [3]武警北京总队医院药剂科,北京100027

出　　处：《中国临床药理学杂志》2022年第24期2946-2949,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(No.81872926);临床合理用药生物特征谱学评价北京市重点实验室基金资助项目(BZ0439)。

摘　　要：目的考察醛氧化酶1(AOX1)在急性淋巴细胞白血病(ALL)中的表达,评估其作为ALL诊断、预后和甲氨蝶呤(MTX)敏感性生物标记物的潜力。方法基于UCSC数据库下载ALL患者和正常人的RNA测序数据,分析AOX1基因在ALL组与正常组中的表达差异。自TARGET数据集获得ALL患者的总生存期(OS)数据,基于AOX1基因表达水平分为AOX1高表达组与低表达组,分析AOX1基因表达高低对ALL患者预后的影响。基于抗癌药物敏感性基因组学数据库预测MTX半数抑制浓度(IC_(50)),分析AOX1基因表达与MTX敏感性的相关性。根据TARGET数据集的RNA测序数据中AOX1基因与N6-甲基腺嘌呤(m^(6)A)甲基化修饰基因表达的相关性,分析m^(6)A修饰在AOX1基因表达调控中的作用。结果ALL组AOX1基因的阳性表达率93.18%(123例/132例),显著低于正常组98.22%(331例/337例,P<0.01),但2组AOX1基因的中位表达分别为-3.11和-3.05,差异无统计学意义(P=0.43)。AOX1高表达组的中位生存时间(26.30个月)显著劣于低表达组(70.30个月,P<0.01)。AOX1基因表达与MTX IC50显著负相关(r=-0.29,P<0.01),与多个m^(6)A修饰基因表达显著正相关。结论AOX1基因在ALL中低表达,与ALL预后和MTX化疗敏感性显著相关,m^(6)A修饰可能是ALL中AOX1基因表达调控的机制之一。ObjectiveTo investigate the expression of Aldehyde Oxidase 1 (AOX1) in acute lymphoblastic leukemia (ALL) and explore its potential as biomarkers for ALL diagnosis,prognosis,and methotrexate (MTX) sensitivity.Method Differential expression analysis of the AOX1 gene in ALL and normal controls was performed based on the RNA sequencing data downloaded from the UCSC database.According to expression of AOX1,patients with ALL were divided into high and low expression groups.Effects of AOX1 expression on the prognosis of ALL were studied based on the overall survival (OS)information obtained from the TARGET database.Associations of AOX1expression with the MTX sensitivity were investigated based on the 50%inhibitory concentration (IC_(50)) of MTX predicted by the Genomics of Drug Sensitivity in Cancer database.The role of N6-methyladenosine(m^(6)A) modification in the regulation of AOX1 expression were explored based on the correlations of AOX1 expression to genes involved in the m^(6)A modification extracted from the RNA sequencing data of the TARGET database.Results The positive expression rate of AOX1 in ALL (93.18%,123 cases/132 cases) was significantly lower than that in normal samples (98.22%,331 cases/337 cases,P<0.01).However,the difference between the median expressions of AOX1 in ALL (-3.11)and normal samples (-3.05) did not achieve statistical significance(P=0.43).The median survival of patients with high expression of AOX1 (26.30 months) was significantly worse than that in patients with low expression of AOX1(70.30 months,P<0.01).AOX1 expression was significantly negatively correlated with MTX IC50(r=-0.29,P<0.01).AOX1 expression had significant positive correlations with many genes involved in the m^(6)A modification.Conclusion AOX1 was low-expressed in ALL and had significant associations with ALL prognosis and MTX sensitivity.The m^(6)A modification might be a mechanism responsible for AOX1 regulation in ALL.

关 键 词：急性淋巴细胞白血病 醛氧化酶1 甲氨蝶呤 RNA修饰 

分 类 号：R97[医药卫生—药品]