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循环微小RNA作为弥漫性大B细胞淋巴瘤的生物标志物:一项前瞻性纵向临床研究试点

Circulating MicroRNAs as Biomarkers in Diffuse Large B-cell Lymphoma: A Pilot Prospective Longitudinal Clinical Study.

作者信息

Bouvy Céline, Wannez Adeline, George Fabienne, Graux Carlos, Chatelain Christian, Dogné Jean-Michel

机构信息

University of Namur, Namur Research Institute for Life Sciences, Namur Thrombosis and Hemostasis Center, Department of Pharmacy, Namur, Belgium.

QUALIblood s.a., Namur, Belgium.

出版信息

Biomark Cancer. 2018 Jun 18;10:1179299X18781095. doi: 10.1177/1179299X18781095. eCollection 2018.

DOI:10.1177/1179299X18781095
PMID:29977116
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6024490/
Abstract

OBJECTIVES

Diffuse large B-cell lymphoma (DLBCL) is highly heterogeneous in terms of phenotype and treatment response in patients. These characteristics make the prognosis difficult to establish and hinder the use of new personalized treatments in clinical practice. In this context, there is currently a need to define new biomarkers enabling a better definition of DLBCL subtypes, prognosis evaluation, and an overview of the resistance to chemotherapeutics. The aim of this study was to evaluate the use of microRNAs found in plasma from patients with DLBCL as biomarkers of tumor evolution in these patients.

METHOD

For this purpose, a plasma biobank was created with samples from patients with DLBCL. The evolution of the level of selected microRNAs during treatment has been studied. A total of 19 patients with DLBCL were included in this pilot mono-centered study and a total of 68 samples were analyzed.

RESULTS

The first step of this study was the selection of the microRNAs to be quantified in all the samples of the biobank and that could potentially be used as biomarkers. To this end, quantification of 377 microRNAs was performed on the plasma samples of 2 selected patients with DLBCL and 1 healthy donor with no history of cancer. Among the 377 microRNAs evaluated, 7 were selected and analyzed in the entire biobank.

CONCLUSIONS

This study highlighted 5 circulating microRNAs whose plasma levels would be worth further investigating for the characterization of DLBCL evolution in patients. MiR-21 and miR-197 had a significant higher plasmatic level in patients with tumors unresponsive to treatment. With a higher plasma level in patients with complete remission, miR-19b, miR-20a, and miR-451 could enable to differentiate, at the remission review, patients with residual tumor, from patients with complete remission.

摘要

目的

弥漫性大B细胞淋巴瘤(DLBCL)在患者的表型和治疗反应方面具有高度异质性。这些特征使得预后难以确定,并阻碍了新的个性化治疗在临床实践中的应用。在此背景下,目前需要定义新的生物标志物,以便更好地定义DLBCL亚型、评估预后以及概述对化疗药物的耐药性。本研究的目的是评估DLBCL患者血浆中发现的微小RNA作为这些患者肿瘤进展生物标志物的用途。

方法

为此,建立了一个血浆生物样本库,其中包含DLBCL患者的样本。研究了所选微小RNA在治疗期间水平的变化。这项单中心试点研究共纳入了19例DLBCL患者,共分析了68个样本。

结果

本研究的第一步是选择要在生物样本库的所有样本中进行定量且可能用作生物标志物的微小RNA。为此,对2例选定的DLBCL患者和1例无癌症病史的健康供体的血浆样本进行了377种微小RNA的定量。在评估的377种微小RNA中,有7种被选出来在整个生物样本库中进行分析。

结论

本研究突出了5种循环微小RNA,其血浆水平值得进一步研究,以用于DLBCL患者病情进展的特征分析。在对治疗无反应的患者中,miR-21和miR-197的血浆水平显著更高。miR-19b、miR-20a和miR-451在完全缓解的患者中血浆水平较高,在缓解复查时能够区分有残留肿瘤的患者和完全缓解的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af7/6024490/9a77192c6a36/10.1177_1179299X18781095-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af7/6024490/9a77192c6a36/10.1177_1179299X18781095-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5af7/6024490/9a77192c6a36/10.1177_1179299X18781095-fig1.jpg

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