细胞外囊泡中的 miRNA 在慢性移植物抗宿主病中的差异表达：一项初步研究。

Differential expression of miRNAs from extracellular vesicles in chronic graft-versus-host disease: A preliminary study.

机构信息

Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, United Kingdom.

出版信息

Adv Clin Exp Med. 2023 May;32(5):539-544. doi: 10.17219/acem/155373.

DOI:10.17219/acem/155373

PMID:36398373

Abstract

BACKGROUND

Chronic graft-versus-host disease (cGvHD) is a complex disorder that typically manifests after allogeneic hematopoietic stem cell transplantation (HSCT). It is a major cause of non-relapse mortality, which makes finding biomarkers associated with its occurrence a priority. Recent studies increasingly indicate that microRNAs (miRNAs, short regulatory RNA molecules) can be used as biomarkers of various disorders. They can circulate in patients' bodies encapsulated within extracellular vesicles (EVs).

OBJECTIVES

To identify miRNAs associated with the occurrence of cGvHD in EVs isolated from the plasma of patients after allogeneic HSCT.

MATERIAL AND METHODS

We performed global miRNA expression profiling in a pilot cohort of 3 cGvHD cases and 4 non-cGvHD patients without disease symptoms 90 days after the transplantation (control group).

RESULTS

The 2 groups were naturally clustered according to their miRNA profiles using unsupervised hierarchical clustering analysis. We identified 3 miRNAs that were differentially expressed in the cGvHD patients compared to the non-cGvHD patients. The levels of hsa-miR-630 and hsa-miR-374b-5p were lower in the cGvHD patients: 4.1-fold (p = 0.002) and 2.7-fold (p = 0.044), respectively. In contrast, the levels of hsa-miR-29c-3p were 5.8-fold higher (p = 0.004).

CONCLUSIONS

Our results suggest that miRNA profiles from plasma EVs may act as markers of cGvHD onset.

摘要

背景

慢性移植物抗宿主病（cGvHD）是一种复杂的疾病，通常在异基因造血干细胞移植（HSCT）后出现。它是导致非复发死亡率的主要原因，因此寻找与其发生相关的生物标志物是当务之急。最近的研究越来越表明，微小 RNA（miRNAs，短调节 RNA 分子）可用作各种疾病的生物标志物。它们可以封装在患者体内的细胞外囊泡（EVs）中循环。

目的

鉴定与异基因 HSCT 后患者血浆中 EVs 分离的 cGvHD 发生相关的 miRNAs。

材料与方法

我们对 3 例 cGvHD 病例和 4 例无疾病症状的非 cGvHD 患者在移植后 90 天的血浆进行了 miRNA 表达谱的初步分析。

结果

使用无监督层次聚类分析，根据 miRNA 谱将 2 组自然聚类。与非 cGvHD 患者相比，我们在 cGvHD 患者中鉴定出 3 个差异表达的 miRNA。hsa-miR-630 和 hsa-miR-374b-5p 的水平在 cGvHD 患者中分别降低了 4.1 倍（p=0.002）和 2.7 倍（p=0.044）。相比之下，hsa-miR-29c-3p 的水平升高了 5.8 倍（p=0.004）。