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HSPG2 overexpression independently predicts poor survival in patients with acute myeloid leukemia.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-06-30 , DOI: 10.1038/s41419-020-2694-7
Xiaojia Zhou 1 , Simin Liang 1 , Qian Zhan 2 , Li Yang 1 , Jianxiang Chi 3 , Li Wang 1
Affiliation  

Heparan sulfate proteoglycan 2 (HSPG2), also known as perlecan, is a large multi-domain extracellular matrix proteoglycan, which contributes to the invasion, metastasis and angiogenesis of solid tumor. However, very little is known about the effect of HSPG2 on acute myeloid leukemia (AML). This study aims to investigate the prognostic value of the HSPG2 gene in terms of overall survival and leukemia-free survival in patients with AML. Bone marrow mononuclear cells (BMMCs) from 4 AML patients and 3 healthy controls were processed for RNA-Sequencing (RNA-seq). The mRNA expression level of HSPG2 in BMMCs and CD34+ hematopoietic stem/progenitor cells (HSPC) obtained from enrolled participants and human leukemic cell lines was detected by RT-qPCR. Then the correlations between the expression of HSPG2 and a variety of important clinical parameters, such as median white blood cell (WBC) count and bone marrow (BM) blasts, were further analyzed. The expression level of HSPG2 was significantly upregulated in AML patients at the time of diagnosis, downregulated after complete remission and then elevated again at relapse. Moreover, HSPG2 expression was associated with median WBC count (P < 0.001), median hemoglobin (P = 0.02), median platelet count (P = 0.001), and BM blasts (P < 0.001) in AML patients. Patients with high HSPG2 expression had both worse overall survival (OS) (P = 0.001) and poorer leukemia-free survival (LFS) (P = 0.047). In the multivariate analysis model, HSPG2 was identified as an independent prognostic biomarker of AML. Taken together, these results indicate that HSPG2 overexpression was associated with poor prognosis in AML patients, and may be a prognostic biomarker and therapeutic target of AML.



中文翻译:

HSPG2过表达独立预测急性髓性白血病患者的不良生存。

硫酸乙酰肝素蛋白聚糖2(HSPG2),也称为perlecan,是一种大型的多域细胞外基质蛋白聚糖,可促进实体瘤的侵袭,转移和血管生成。但是,关于HSPG2对急性髓细胞性白血病(AML)的影响知之甚少。这项研究旨在调查HSPG2基因在AML患者的总生存率和无白血病生存率方面的预后价值。对来自4名AML患者和3名健康对照的骨髓单核细胞(BMMC)进行RNA测序(RNA-seq)。HSPG2在BMMC和CD34 +中的mRNA表达水平通过RT-qPCR检测从入组受试者和人类白血病细胞系获得的造血干/祖细胞(HSPC)。然后,进一步分析了HSPG2的表达与各种重要临床参数之间的相关性,例如中值白细胞(WBC)计数和骨髓(BM)母细胞。在诊断时,AML患者中HSPG2的表达水平显着上调,完全缓解后则下调,然后在复发时再次升高。此外,HSPG2的表达与中位白细胞计数(P  <0.001),中位血红蛋白(P  = 0.02),血小板中位数(P  = 0.001)和BM母细胞(P <0.001)。HSPG2高表达的患者的总生存期(OS) 较差(P = 0.001),无白血病生存期(LFS)较差(P  = 0.047)。在多变量分析模型中,HSPG2被确定为AML的独立预后生物标志物。综上所述,这些结果表明HSPG2过表达与AML患者的不良预后有关,并且可能是AML的预后生物标志物和治疗靶标。

更新日期:2020-06-30
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