血清衍生细胞外囊泡中的 microRNA-155 作为血液系统恶性肿瘤的潜在生物标志物 - 简短报告。
MicroRNA-155 in serum-derived extracellular vesicles as a potential biomarker for hematologic malignancies - a short report.
机构信息
Laboratory of Preclinical and Translational Research, IRCCS-Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Potenza, Italy.
Institute for the Study of the Structure of Matter, National Research Council (CNR), Rome, Italy.
出版信息
Cell Oncol (Dordr). 2017 Feb;40(1):97-103. doi: 10.1007/s13402-016-0300-x. Epub 2016 Oct 19.
PURPOSE
The use of extracellular vesicles (EVs) from body fluids as "liquid biopsies" is emerging as a promising approach for the diagnosis, prognosis and therapeutic monitoring of cancer patients. MicroRNA-155 (miR155), a non-coding transcript of the B-cell integration cluster (BIC) gene, has been reported to play a critical role in the pathogenesis of several types of hematologic malignancies (HMs) in which high miR155 levels have been found. At yet, however, the EV miR155 level and its putative clinical relevance in sera of HM patients have not been reported.
METHODS
EVs from sera of representative patients with eight different HMs and healthy subjects (controls) were isolated using differential centrifugation. The identity and quality of the EVs were verified by atomic force and transmission electron microscopy. The EV miR155 levels were measured by quantitative RT-PCR. The sensitivity, specificity and area under the curve (AUC) of differences in EV miR155 levels were determined using ROC curve analyses.
RESULTS
We found that the EV miR155 levels were significantly higher in chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and Waldenström's macroglobulinemia (WM) cases compared to controls. Conversely, we found that the EV miR155 levels were significantly lower in myelodysplastic syndrome (MDS) and multiple myeloma (MM) cases. No differences were found in follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) or Hodgkin's Lymphoma (HL) cases compared to controls. EV miR155 ROC curve analyses revealed significantly different patterns in CLL and AML cases compared to controls, and in AML cases compared to MDS cases (p = 0.004, p = 0.01 and p = 0.04, respectively). In addition, we found that high EV miR155 levels correlated with high white blood cell counts in AML patients.
CONCLUSION
Our data indicate that EV miR155 may serve as an attractive new, non-invasive diagnostic biomarker in human hematologic malignancies.
目的
利用体液中的细胞外囊泡（EVs）作为“液体活检”，正成为诊断、预后和癌症患者治疗监测的一种有前途的方法。微 RNA-155（miR155）是 B 细胞整合簇（BIC）基因的非编码转录本，据报道，在几种血液恶性肿瘤（HM）的发病机制中发挥关键作用，其中发现高 miR155 水平。然而，HM 患者血清中 EV miR155 水平及其潜在临床相关性尚未报道。
方法
使用差速离心法从代表 8 种不同 HM 患者和健康受试者（对照）的血清中分离 EVs。通过原子力和透射电子显微镜验证 EVs 的身份和质量。通过定量 RT-PCR 测量 EV miR155 水平。使用 ROC 曲线分析确定 EV miR155 水平差异的灵敏度、特异性和曲线下面积（AUC）。
结果
我们发现慢性淋巴细胞白血病（CLL）、急性髓系白血病（AML）和华氏巨球蛋白血症（WM）病例的 EV miR155 水平明显高于对照组。相反，我们发现骨髓增生异常综合征（MDS）和多发性骨髓瘤（MM）病例的 EV miR155 水平明显较低。与对照组相比，滤泡性淋巴瘤（FL）、弥漫性大 B 细胞淋巴瘤（DLBCL）或霍奇金淋巴瘤（HL）病例无差异。与对照组相比，CLL 和 AML 病例的 EV miR155 ROC 曲线分析显示出明显不同的模式，与 MDS 病例相比，AML 病例也显示出明显不同的模式（p=0.004、p=0.01 和 p=0.04）。此外，我们发现 AML 患者中高 EV miR155 水平与白细胞计数高相关。
结论
我们的数据表明，EV miR155 可能作为一种有吸引力的新型非侵入性诊断生物标志物，用于人类血液恶性肿瘤。
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