IGF2BP2 Overexpression Indicates Poor Survival in Patients with Acute Myelocytic Leukemia
IGF2BP2 Overexpression Indicates Poor Survival in Patients with Acute Myelocytic Leukemia
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IGF2BP2 过度表达表明急性髓细胞白血病患者的生存率较差
DOI：
10.1159/000495719
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Chen, Zhigang
中科院分区：
文献类型：
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作者：
He, Xin;Li, Wenlu;Chen, Zhigang
背景/目的：IGF 2BP 2已被报道在各种实体癌中作为癌基因。然而，IGF 2BP 2在急性髓细胞白血病（AML）中的作用仍然未知。方法：应用Gene Omnibus数据库检测IGF 2BP 2在AML患者和健康对照组中的表达。此外，通过Ficoll密度离心法制备这两个群体的原代细胞。采用RT-qPCR和western blot检测IGF 2BP 2在这两个群体的原代细胞中的表达。Meta分析IGF 2BP 2与预后的关系。基于慢病毒的shRNA用于敲低AML细胞系KG-1a和Kasumi中的IGF 2BP 2。结果：我们检索了公共数据库Gene Omnibus，并分析了AML和健康人群中IGF 2BP 2的表达。结果表明，IGF 2BP 2在AML患者中过表达。为了在新鲜的人类样本中验证这一现象，我们比较了10名AML患者和10名健康对照的原代细胞中IGF 2BP 2的表达，发现IGF 2BP 2的表达在AML原代细胞中上调。更重要的是，我们观察到IGF 2BP 2表达与CEBPA突变状态呈负相关，这是预后良好的指标（RR=0.648，p=0.0001）。此外，IGF 2BP 2表达与不良预后因素正相关，如FLT 3-ITD突变（RR=1.198，p=0.0009）和IDH 1突变（RR=1.354，p=0.0003），以及中等和不良细胞遗传学风险（RR=1.214，p=0.0026）。为了评估IGF 2BP 2在AML中的预后价值，我们进一步对8项研究（包括1731例患者）进行了荟萃分析，发现IGF 2BP 2过表达与AML患者的总生存率较差相关[HR=1.31（1.16-1.49）; p = 0.00]。此外，我们进行了基因Omnibus和基因集富集分析，发现IGF 2BP 2调控的基因主要富集在细胞增殖中。通过4种不同的shRNA载体敲低IGF 2BP 2显著抑制两种AML细胞系KG-1a和Kasumi的生长。结论：IGF 2BP 2可作为预测AML预后的生物标志物，并可作为AML治疗的潜在靶点。
Background/Aims: IGF2BP2 has been reported to serve as an oncogene in various solid cancers. However, the role of IGF2BP2 in acute myelocytic leukemia (AML) is still unknown. Methods: Public databases Gene Omnibus was used to evaluate the expression of IGF2BP2 in AML patients and healthy controls. In addition, primary cells from these two populations were prepared by Ficoll density centrifugation. Rt-qPCR and western blot were used to detect IGF2BP2 expression in the primary cells from these two populations. Meta-analysis was performed to evaluate the association of IGF2BP2 and prognosis. Lentivirus-based shRNAs were used to knock down IGF2BP2 in AML cell lines KG-1a and Kasumi. Results: We searched the public database Gene Omnibus and analyzed IGF2BP2 expression in both AML and healthy populations. The results showed that IGF2BP2 was overexpressed in AML patients. To verify this phenomenon in fresh human samples, we compared the expression of IGF2BP2 in primary cells from 10 AML patients and 10 healthy controls and found that the expression of IGF2BP2 was upregulated in AML primary cells. More importantly, we observed that IGF2BP2 expression was negatively correlated with the CEBPA mutation status, which is an indicator of good prognosis (RR=0.648, p=0.0001). In addition, IGF2BP2 expression was positively associated with poor prognostic factors, such as the FLT3-ITD mutation (RR=1.198, p=0.0009) and IDH1 mutation (RR=1.354, p=0.0003), as well as intermediate and poor cytogenetic risk (RR=1.214, p=0.0026). To evaluate the prognostic value of IGF2BP2 in AML, we further performed a meta-analysis of 8 studies consisting of 1731 patients and found that IGF2BP2 overexpression was correlated with worse overall survival in AML patients [HR=1.31(1.16-1.49); p = 0.00]. Furthermore, we performed Gene Omnibus and Gene Set Enrichment analyses and found that the genes regulated by IGF2BP2 were mainly enriched in cell proliferation. IGF2BP2 knockdown by 4 different shRNA vectors significantly inhibited the growth of two AML cell lines, KG-1a and Kasumi. Conclusion: Thus, IGF2BP2 may serve as a biomarker to predict the prognosis of AML and as a potential target in AML.