Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
Ann Hematol. 2021 Oct;100(10):2621-2631. doi: 10.1007/s00277-021-04573-1. Epub 2021 Jul 11.
Currently, acute graft-versus-host disease (aGVHD) diagnosis is based on clinical features and pathological findings. Until now, there is no non-invasive diagnostic test for aGVHD. MicroRNAs may act as promising predictive, diagnostic, or prognostic biomarkers for aGVHD. The purpose of the current study was to validate circulating microRNAs as diagnostic biomarkers to assist clinicians in promptly diagnosing aGVHD, so that treatment can be initiated earlier. In the present study, we evaluated six microRNAs (miR-455-3p, miR-5787, miR-6729-5p, miR-6776-5p, miR-548a-3p, and miR-6732-5p) selected from miRNA array data in 40 aGVHD patients compared to 40 non-GVHD patients with RT-qPCR. Target genes of differentially expressed microRNAs (DEMs) were predicted using Targetscan, miRanda, miRDB, miRWalk, PICTAR5, miRmap, DIANA, and miRTarBase algorithms, and their functions were analyzed using EnrichNet, Metascape, and DIANA-miRPath databases. The expressions of plasma miR-455-3p and miR-5787 were significantly downregulated, whereas miR-548a-3p was significantly upregulated in aGVHD patients compared to non-GVHD patients. Moreover, DEMs showed potentially high diagnostic accuracy for aGVHD. In silico analysis of DEMs provided valuable information on the role of DEMs in GVHD, immune regulation, and inflammatory response. Our study suggested that miR-455-3p, miR-5787, and miR-548a-3p could be used as potential noninvasive biomarkers in the diagnosis of aGVHD in addition to possible therapeutic targets in aGVHD.
目前，急性移植物抗宿主病（aGVHD）的诊断基于临床特征和病理发现。到目前为止，还没有用于诊断 aGVHD 的非侵入性诊断测试。microRNAs 可能作为有前途的预测、诊断或预后生物标志物用于 aGVHD。本研究的目的是验证循环 microRNAs 是否可作为诊断生物标志物，以帮助临床医生及时诊断 aGVHD，从而更早开始治疗。在本研究中，我们通过 RT-qPCR 评估了 40 名 aGVHD 患者和 40 名非 GVHD 患者中 microRNA 芯片数据中选择的 6 个 microRNAs（miR-455-3p、miR-5787、miR-6729-5p、miR-6776-5p、miR-548a-3p 和 miR-6732-5p）的表达。使用 Targetscan、miRanda、miRDB、miRWalk、PICTAR5、miRmap、DIANA 和 miRTarBase 算法预测差异表达 microRNAs（DEMs）的靶基因，并使用 EnrichNet、Metascape 和 DIANA-miRPath 数据库分析其功能。与非 GVHD 患者相比，aGVHD 患者的血浆 miR-455-3p 和 miR-5787 表达明显下调，而 miR-548a-3p 表达明显上调。此外，DEMs 显示出对 aGVHD 具有潜在的高诊断准确性。DEMs 的计算分析提供了关于 DEMs 在 GVHD、免疫调节和炎症反应中的作用的有价值信息。我们的研究表明，miR-455-3p、miR-5787 和 miR-548a-3p 除了可能成为 aGVHD 的治疗靶点外，还可作为 aGVHD 诊断的潜在非侵入性生物标志物。
