MicroRNA-155-5p Overexpression in Peripheral Blood Mononuclear Cells of Chronic Lymphocytic Leukemia Patients Is a Novel, Independent Molecular Biomarker of Poor Prognosis.

MicroRNA-155-5p Overexpression in Peripheral Blood Mononuclear Cells of Chronic Lymphocytic Leukemia Patients Is a Novel, Independent Molecular Biomarker of Poor Prognosis.
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DOI:
10.1155/2017/2046545
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发表时间:
2017
期刊:
影响因子:
--
通讯作者:
Scorilas A
Scorilas A
中科院分区:
医学4区
文献类型:
--
作者:
Papageorgiou SG;Kontos CK;Diamantopoulos MA;Bouchla A;Glezou E;Bazani E;Pappa V;Scorilas A

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MicroRNA-155-5p(miR-155-5p)是一种促炎症、致癌的miRNA,参与多种生理过程,包括造血、免疫、炎症和细胞系分化。它调节重要的转录因子,如E2F2、缺氧诱导因子1(HIF1)和FOX03。近年来,miR-155-5p表达异常与慢性淋巴细胞白血病(CLL)的发病机制有关。在本研究中,我们探讨miR-155-5p在慢性淋巴细胞性白血病中的潜在诊断和预后价值。为了实现我们的目标,我们从88例慢性淋巴细胞性白血病患者和36名非白血病献血员的外周血单个核细胞(PBMC)中提取总RNA,并对总RNA进行多聚腺苷酸化和逆转录。接下来,我们使用内部开发的实时定量聚合酶链式反应方法对miR-155-5p水平进行量化,然后进行广泛的生物统计分析。由此可见,miR-155-5p在慢性粒细胞白血病患者外周血单核细胞中显著过表达,并可将其与非白血病患者区分开来。Kaplan-Meier OS分析和Bootstrap单因素Cox回归分析显示,miR-155-5p的高表达预示着慢性淋巴细胞性白血病患者的OS较差(p<0.001)。有趣的是,miR-155-5p的过度表达在CLL患者中仍然具有不利的预后作用,根据已确定的预后因素[CD38表达和免疫球蛋白重链可变区(IGHV)的突变状态]进行分层。因此,miR-155-5p有望成为CLL预后不良的独立分子标志物。
MicroRNA-155-5p (miR-155-5p) is a proinflammatory, oncogenic miRNA, involved in various physiological processes, including hematopoiesis, immunity, inflammation, and cell lineage differentiation. It regulates important transcription factors, such as E2F2, hypoxia-inducible factor 1 (HIF1), and FOXO3. Recently, the dysregulation of miR-155-5p expression has been linked to chronic lymphocytic leukemia (CLL) pathogenesis. In this research study, we investigated the potential diagnostic and prognostic value of miR-155-5p in CLL. To achieve our goal, we isolated total RNA from peripheral blood mononuclear cells (PBMCs) collected from 88 CLL patients and 36 nonleukemic blood donors and performed polyadenylation of total RNA and reverse transcription. Next, we quantified miR-155-5p levels using an in-house-developed real-time quantitative PCR method, before proceeding to extensive biostatistical analysis. Thus, it appears that miR-155-5p is significantly overexpressed in PBMCs of CLL patients and can distinguish them from nonleukemic population. Kaplan-Meier OS analysis and bootstrap univariate Cox regression showed that high miR-155-5p expression predicts inferior OS for CLL patients (p < 0.001). Interestingly, miR-155-5p overexpression retains its unfavorable prognostic role in CLL patients stratified according to established prognostic factors [CD38 expression and mutational status of the immunoglobulin heavy chain variable region (IGHV)]. Thus, miR-155-5p appears as a promising, independent molecular biomarker of unfavorable prognosis in CLL.
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