ENPP2在急性髓细胞白血病中的表达与临床意义

The expression and clinical significance of ENPP2 in acute myeloid leukemia

目的分析外核苷酸焦磷酸酶/磷酸二酯酶家族成员2(ENPP2)在急性髓细胞白血病(AML)中的表达及临床意义,并初步探索其潜在分子机制。方法使用GTEx数据库分析ENPP2在不同正常组织中的表达谱,使用R studio与Graphpad分析GEO与TCGA数据库中ENPP2的表达、基因组突变及患者生存,并进一步通过GSEA富集软件分析ENPP2高低表达组信号通路富集状态。结果ENPP2在正常组织中主要高表达于脂肪、脑与子宫组织;在急性髓细胞白血病患者组织中的表达高于正常人对照组,且在187例TCGA基因组数据中有约0. 5%患者存在基因扩增,无基因突变与缺失;ENPP2在复发AML中的表达显著高于原发患者,且其高表达与AML患者不良预后相关;基因富集分析显示ENPP2与自身免疫性疾病、细胞因子受体活化呈正相关,与DNA复制、细胞周期等通路呈负相关,且可能参与维甲酸、糖皮质激素治疗过程。结论 ENPP2在AML患者中高表达且与患者复发及不良预后相关,其主要分子机制可能与自身免疫反应以及药物治疗反应相关,ENPP2可能是治疗AML的潜在新靶点。

Objective To analyze the expression and clinical significance of exonucleotide pyrophosphatase/ phosphodiesterase family member 2 ( ENPP2) in acute myeloid leukemia ( AML), and to explore its potential molecular mechanism. Methods The expression profiles of ENPP2 in different normal tissues was analyzed with GTEx database. Rstudio and Graphpad were used to analyze ENPP2 expression, genomic mutations and survival curve in data from GEO and TCGA databases, and the signaling pathway associated with ENPP2 expression were further analyzed with GSEA enrichment software. Results In normal tissues, ENPP2 was mainly expressed in fat, brain and uterus;the expression in acute myeloid leukemia tissues was higher than that in donors. Only 0. 5% of patients in 187 TCGA genomic data had gene amplification ,there was no gene mutations and deletions. ENPP2 expression in recurrent AML was significantly higher than primary patients, and its high expression was associated with poor prognosis. Gene enrichment analysis shows high ENPP2 group isenriched in autoimmune diseases, cytokine receptor activation pathway, and low ENPP2 was enriched in DNA replication, cell cycle pathways. ENPP2 was also involved in the pathway that associated with retinoic acid and glucocorticoids treatment. Conclusions ENPP2 is highly expressed in AML patients and is associated with recurrence and poor prognosis of AML. The main molecular mechanism of ENPP2 in AML may be related to autoimmune response and drug treatment response, ENPP2 is a potential therapy target of AML.