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通过循环血浆 miR-638、miR-6511b-5p、miR-3613-5p、miR-455-3p、miR-5787 和 miR-548a-3p 诊断异基因造血干细胞移植后的皮肤急性移植物抗宿主病:潜在的非侵入性生物标志物。

Diagnosis of Cutaneous Acute Graft‑Versus‑Host Disease Through Circulating Plasma miR-638, miR-6511b-5p, miR-3613-5p, miR-455-3p, miR-5787, and miR-548a-3p as Prospective Noninvasive Biomarkers Following Allogeneic Hematopoietic Stem Cell Transplantation.

机构信息

Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology, and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Clin Transplant. 2024 Jun;38(6):e15371. doi: 10.1111/ctr.15371.

Abstract

BACKGROUND

There are currently no laboratory tests that can accurately predict the likelihood of developing acute graft-versus-host disease (aGVHD), a patient's response to treatment, or their survival chance. This research aimed to establish circulating miRNAs as diagnostic, prognostic, or predictive biomarkers of aGVHD.

METHODS

In a prospective cohort, we studied the incidence of cutaneous aGVHD in AML patients undergoing allo-HSCT at Shariati Hospital in Tehran, Iran during 2020-2023. Patients with cutaneous aGVHD were labeled as the case group, while patients without cutaneous aGVHD were selected as the control group. Accordingly, the expression levels of six significant miRNAs (miR-638, miR-6511b-5p, miR-3613-5p, miR-455-3p, miR-5787, miR-548a-3p) were evaluated by quantitative reverse transcription-polymerase chain reaction (RTqPCR) in three different time-points: before transplantation, on day 14 and day 21 after transplantation.

RESULTS

The levels of plasma miR-455-3p, miR-5787, miR-638, and miR-3613-5p were significantly downregulated, while miR-548a-3p, and miR-6511b-5p were significantly upregulated in individuals with cutaneous aGVHD in comparison to patients without GVHD. Additionally, the possibility for great diagnostic accuracy for cutaneous aGVHD was revealed by ROC curve analysis of differentially expressed miRNAs (DEMs).

CONCLUSION

The study findings encourage us to hypothesize that the aforementioned miRNAs may contribute to the predominance of aGVHD, particularly low-grade cutaneous aGVHD.

摘要

背景

目前尚无实验室检测手段能够准确预测急性移植物抗宿主病(aGVHD)的发生概率、患者对治疗的反应或生存机会。本研究旨在确定循环 miRNA 作为 aGVHD 的诊断、预后或预测生物标志物。

方法

在一项前瞻性队列研究中,我们研究了 2020 年至 2023 年期间在伊朗德黑兰 Shariati 医院接受异基因造血干细胞移植(allo-HSCT)的 AML 患者中皮肤 aGVHD 的发生率。患有皮肤 aGVHD 的患者被标记为病例组,而未患有皮肤 aGVHD 的患者被选为对照组。相应地,通过定量逆转录-聚合酶链反应(RTqPCR)在三个不同时间点(移植前、移植后第 14 天和第 21 天)评估了 6 种显著 miRNA(miR-638、miR-6511b-5p、miR-3613-5p、miR-455-3p、miR-5787、miR-548a-3p)的表达水平。

结果

与无 GVHD 患者相比,患有皮肤 aGVHD 的个体血浆 miR-455-3p、miR-5787、miR-638 和 miR-3613-5p 的水平明显下调,而 miR-548a-3p 和 miR-6511b-5p 的水平明显上调。此外,通过差异表达 miRNA(DEM)的 ROC 曲线分析,揭示了这些 miRNA 具有出色的皮肤 aGVHD 诊断准确性的可能性。

结论

研究结果促使我们假设上述 miRNA 可能导致 aGVHD 的发生,特别是低级别皮肤 aGVHD。

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