High Expression of VAV Gene Family Predicts Poor Prognosis of Acute Myeloid Leukemia.

High Expression of VAV Gene Family Predicts Poor Prognosis of Acute Myeloid Leukemia.
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DOI:
10.1177/15330338211065877
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发表时间:
2021-01
影响因子:
2.8
通讯作者:
Liu W
Liu W
中科院分区:
医学4区
文献类型:
--
作者:
Mu D;Long S;Guo L;Liu W

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目的:VAV 家族基因(VAV1、VAV2 和 VAV3)与多种癌症的预后相关;然而,它们尚未在急性髓系白血病(AML)中进行评估。本研究通过单中心研究结合生物信息学分析评估了 VAV 表达在 AML 中的预后价值。方法:使用各种数据库(包括 GEPIA、CCLE、EMBL-EBI、UALCAN、cBioPortal、STRING 和 DAVID)研究 AML 患者中 VAV 的表达和预后价值。我们中心收集了 35 名 AML(非 M3 亚型)患者和 13 名健康个体的血液样本。通过实时定量PCR(RT-qPCR)和蛋白质印迹法检测VAV表达水平。临床数据来自医疗记录。结果:基于多个数据库的数据,AML中VAV1、VAV2和VAV3的表达水平显着高于对照组织(P < 0.05)。 RT-qPCR和western blotting结果显示,AML患者VAV的mRNA和蛋白表达水平均高于对照组(P < 0.05)。 VAV1 高表达的 AML 患者完全缓解率低于 VAV1 低表达的患者,且风险较高(P < 0.05)。高水平的 VAV2、VAV3 和 VAV1 与较差的总生存率相关,并且这种关系对于 VAV1 而言显着 (P < 0.05)。与 VAV1 相关的基因(例如 SIPA1、SH2D3C 和 HMHA1)的高表达水平也与 AML 的不良预后有关。功能和通路富集分析表明,VAV 家族对 AML 的贡献可能是由 NF-κB、cAMP 和其他通路介导的。结论:VAVs在AML中高表达。特别是,VAV1 具有预后价值,是 AML 有前途的治疗靶点。
Objectives: VAV family genes (VAV1, VAV2, and VAV3) are associated with prognosis in various cancers; however, they have not been evaluated in acute myeloid leukemia (AML). In this study, the prognostic value of VAV expression in AML was evaluated by a single-center study in combination with bioinformatics analyses. Methods: The expression and prognostic value of VAVs in patients with AML were investigated using various databases, including GEPIA, CCLE, EMBL-EBI, UALCAN, cBioPortal, STRING, and DAVID. Blood samples from 35 patients with AML (non-M3 subtype) and 13 benigh individuals were collected at our center. VAV expression levels were detected by real-time quantitative PCR (RT-qPCR) and western blotting. Clinical data were derived from medical records. Results: Based on data from multiple databases, the expression levels of VAV1, VAV2, and VAV3 were significantly higher in AML than in control tissues (P < 0.05). RT-qPCR and western blotting results showed that VAV expression in mRNA and protein levels were higher in patients with AML that in the control group (P < 0.05). Complete remission rates were lower and risks were higher in patients with AML with high VAV1 expression than with low VAV1 expression (P < 0.05). High levels of VAV2, VAV3, and VAV1 were related to a poor overall survival, and this relationship was significant for VAV1 (P < 0.05). High expression levels of genes correlated with VAV1, such as SIPA1, SH2D3C, and HMHA1 were also related to a poor prognosis in AML. Functional and pathways enrichment analyses indicated that the contribution of the VAV family to AML may be mediated by the NF-κB, cAMP, and other pathways. Conclusion: VAVs were highly expressed in AML. In particular, VAV1 has prognostic value and is a promising therapeutic target for AML.
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