用于子痫前期早期无创诊断的基于血液的 miRNA 特征。

A blood-based miRNA signature for early non-invasive diagnosis of preeclampsia.

机构信息

Department of Gynecology and Obstetrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.

School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.

出版信息

BMC Med. 2022 Sep 13;20(1):303. doi: 10.1186/s12916-022-02495-x.

DOI:10.1186/s12916-022-02495-x

PMID:36096786

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9469544/

Abstract

BACKGROUND

Preeclampsia (PE) is a multisystemic maternal syndrome with substantial maternal and fetal morbidity and mortality. Currently, there is no clinically viable non-invasive biomarker assay for early detection, thus limiting the effective prevention and therapeutic strategies for PE.

METHODS

We conducted a discovery-training-validation three-phase retrospective and prospective study with cross-platform and multicenter cohorts. The initial biomarkers were discovered and verified in tissue specimens by small RNA sequencing and qRT-PCR. A miRNA signature (miR2PE-score) was developed using Firth's bias-reduced logistic regression analysis and subsequently validated in two independent multinational retrospective cohorts and two prospective plasma cohorts.

RESULTS

We initially identified five PE-associated differentially expressed miRNAs from miRNA sequencing data and subsequently validated two miRNAs (miR-196b-5p and miR-584-5p) as robust biomarkers by association analysis with clinical characteristics and qRT-PCR in tissue specimens in the discovery phase. Using Firth's bias-reduced logistic regression analysis, we developed the miR2PE-score for the early detection of PE. The miR2PE-score showed a high diagnostic performance with an area under the receiver operating characteristic curve (AUROC) of 0.920, 0.848, 0.864, and 0.812 in training, internal, and two external validation cross-platform and multicenter cohorts, respectively. Finally, we demonstrated the non-invasive diagnostic performance of the miR2PE-score in two prospective plasma cohorts with AUROC of 0.933 and 0.787. Furthermore, the miR2PE-score revealed superior performance in non-invasive diagnosis compared with previously published miRNA biomarkers.

CONCLUSIONS

We developed and validated a novel and robust blood-based miRNA signature, which may serve as a promising clinically applicable non-invasive tool for the early detection of PE.

摘要

背景

子痫前期（PE）是一种多系统的母体综合征，对母婴都有较大的发病率和死亡率。目前，临床上尚无可行的非侵入性生物标志物检测方法用于早期检测，因此限制了针对 PE 的有效预防和治疗策略。

方法

我们进行了一项具有跨平台和多中心队列的回顾性和前瞻性三阶段发现-训练-验证研究。通过小 RNA 测序和 qRT-PCR 在组织标本中发现和验证初始生物标志物。使用 Firth 偏置减少逻辑回归分析开发 miRNA 特征（miR2PE-评分），并随后在两个独立的多国回顾性队列和两个前瞻性血浆队列中进行验证。

结果

我们最初从 miRNA 测序数据中鉴定出五个与 PE 相关的差异表达 miRNA，随后通过与临床特征的关联分析和组织标本中的 qRT-PCR 验证了两个 miRNA（miR-196b-5p 和 miR-584-5p）作为稳健的生物标志物。使用 Firth 偏置减少逻辑回归分析，我们开发了用于 PE 早期检测的 miR2PE-评分。miR2PE-评分在训练、内部和两个外部验证跨平台和多中心队列中的 AUC 值分别为 0.920、0.848、0.864 和 0.812，具有较高的诊断性能。最后，我们在两个前瞻性血浆队列中证明了 miR2PE-评分的非侵入性诊断性能，AUC 值分别为 0.933 和 0.787。此外，miR2PE-评分在非侵入性诊断方面表现优于以前发表的 miRNA 生物标志物。