Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Medicine, Haukeland University Hospital, Bergen, Norway; and.
Blood Adv. 2022 Sep 27;6(18):5295-5306. doi: 10.1182/bloodadvances.2021005930.
Chronic graft-versus-host disease (cGVHD) is the most common long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). During the last decade, the interest of micro RNAs (miRNAs) in the pathophysiological process of cGVHD has increased. The objectives of this study were to investigate a wide range of serum miRNAs in allografted patients and identify associations between miRNAs and cGVHD. The study included 79 allotransplanted adults, where serum samples were obtained 1 year after the allo-HSCT, and miRNA profiling analysis in serum was performed. Fifty of the 79 patients (63%) had signs of cGVHD at the 1-year post-allo-HSCT control. miRNA sequencing analysis revealed 1380 different miRNAs detected for at least 1 patient, whereas 233 miRNAs (17%) were detected in >70 patients. We identified 10 miRNAs that differed significantly between patients with and without cGVHD (P < .005; false discovery rate <0.1), and all of these miRNAs were detected for >75 of the patients. Furthermore, 5 distinct miRNAs, miR-365-3p, miR-148-3p, miR-122-5p, miR-378-3p, and miR-192-5p, were found to be particularly associated with cGVHD in our analysis and were validated by receiver operating characteristics analysis. Based on only 3 miRNAs, miR-365-3p, miR-148-3p, and miR-378-3p, we developed a miRNA signature that, by bioinformatic approaches and linear regression model, utterly improved our potential diagnostic biomarker model for cGVHD. We conclude that miRNAs are differently expressed among patients with and without cGVHD, although further and larger studies are needed to validate our present findings.
慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植(allo-HSCT)后最常见的长期并发症。在过去十年中,miRNAs 在 cGVHD 的病理生理过程中的作用引起了人们的兴趣。本研究的目的是研究广泛的血清 miRNAs 在同种异体移植患者中的表达,并确定 miRNA 与 cGVHD 之间的关联。该研究纳入了 79 例接受 allo-HSCT 的成年患者,在 allo-HSCT 后 1 年采集血清样本,并进行血清 miRNA 谱分析。79 例患者中有 50 例(63%)在 allo-HSCT 后 1 年的对照中出现 cGVHD 迹象。miRNA 测序分析显示,至少有 1 例患者检测到 1380 种不同的 miRNA,而 233 种 miRNA(17%)在>70 例患者中检测到。我们发现,cGVHD 患者与无 cGVHD 患者之间存在 10 种 miRNA 显著差异(P<0.005;假发现率<0.1),所有这些 miRNA 在>75 例患者中均有检测到。此外,在我们的分析中,miR-365-3p、miR-148-3p、miR-122-5p、miR-378-3p 和 miR-192-5p 这 5 种独特的 miRNA 与 cGVHD 特别相关,并通过接受者操作特征分析得到验证。基于仅 3 种 miRNA(miR-365-3p、miR-148-3p 和 miR-378-3p),我们开发了一个 miRNA 特征,通过生物信息学方法和线性回归模型,极大地改进了我们用于诊断 cGVHD 的潜在生物标志物模型。我们得出结论,miRNAs 在患有和不患有 cGVHD 的患者中表达不同,尽管需要进一步和更大的研究来验证我们目前的发现。