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循环 miR-122-5p、miR-92a-3p 和 miR-18a-5p 作为人类肝移植随访中的潜在生物标志物。

Circulating miR-122-5p, miR-92a-3p, and miR-18a-5p as Potential Biomarkers in Human Liver Transplantation Follow-Up.

机构信息

DIMEC-Department of Medicine and Surgery, University of Bologna, Via S. Giacomo 12, 40126 Bologna, Italy.

Interdepartmental Center, Alma Mater Research Institute on Global Challenges and Climate Change (Alma Climate), University of Bologna, 40126 Bologna, Italy.

出版信息

Int J Mol Sci. 2023 Feb 9;24(4):3457. doi: 10.3390/ijms24043457.

Abstract

The requirement of blood-circulating sensitive biomarkers for monitoring liver transplant (LT) is currently a necessary step aiming at the reduction of standard invasive protocols, such as liver biopsy. In this respect, the main objective of this study is to assess circulating microRNA (c-miR) changes in recipients' blood before and after LT and to correlate their blood levels with gold standard biomarkers and with outcomes such as rejection or complications after graft. An miR profile was initially performed; then, the most deregulated miRs were validated by RT-qPCR in 14 recipients pre- and post-LT and compared to a control group of 24 nontransplanted healthy subjects. MiR-122-5p, miR-92a-3p, miR-18a-5p, and miR-30c-5p, identified in the validation phase, were also analyzed considering an additional 19 serum samples collected from LT recipients and focusing on different follow-up (FU) times. The results showed significant, FU-related changes in c-miRs. In particular, miR-122-5p, miR-92a-3p, and miR-18a-5p revealed the same trend after transplantation and an increase in their level was found in patients with complications, independently from FU times. Conversely, the variations in the standard haemato-biochemical parameters for liver function assessment were not significant in the same FU period, confirming the importance of c-miRs as potential noninvasive biomarkers for monitoring patients' outcomes.

摘要

目前,监测肝移植 (LT) 的循环敏感生物标志物的要求是减少标准侵入性方案(如肝活检)的必要步骤。在这方面,本研究的主要目的是评估 LT 前后受者血液中的循环 microRNA (c-miR) 变化,并将其血液水平与金标准生物标志物以及排斥反应或移植物后并发症等结果相关联。首先进行了 miR 谱分析;然后,在 14 名 LT 受者的术前和术后通过 RT-qPCR 验证了最失调的 miRs,并与 24 名未移植的健康对照者进行了比较。在验证阶段鉴定出的 miR-122-5p、miR-92a-3p、miR-18a-5p 和 miR-30c-5p 也在考虑来自 LT 受者的另外 19 个血清样本时进行了分析,并重点关注不同的随访 (FU) 时间。结果显示 c-miRs 存在显著的 FU 相关变化。特别是 miR-122-5p、miR-92a-3p 和 miR-18a-5p 在移植后呈现出相同的趋势,并且在并发症患者中发现它们的水平增加,与 FU 时间无关。相反,在同一 FU 期间,肝功能评估的标准血液生化参数的变化不显著,这证实了 c-miRs 作为监测患者结果的潜在非侵入性生物标志物的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c4/9962619/9e95b82e5b8a/ijms-24-03457-g001.jpg

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