羊水蛋白质组分析鉴定出 IL1RL1、APOE 和 NECTIN4 是早产的新生物标志物。

Amniotic fluid proteomic analysis identifies IL1RL1, APOE, and NECTIN4 as new biomarkers for preterm birth.

机构信息

Yunnan Provincial Key Laboratory of Public Health and Biosafety, Kunming Medical University, 1168 West Chunrong Road, Chenggong District, Kunming, 650500, Yunnan, P.R. China.

Department of Obstetrics, First People's Hospital of Qujing City, 1 Garden Road, Qilin District, Qujing, 655000, Qujing, Yunnan, P.R. China.

出版信息

BMC Pregnancy Childbirth. 2024 Aug 12;24(1):530. doi: 10.1186/s12884-024-06734-2.

DOI:10.1186/s12884-024-06734-2

PMID:39134987

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11321064/

Abstract

BACKGROUND

Despite extensive research, the identification of effective biomarkers for early prediction of preterm birth (PTB) continues to be a challenging endeavor. This study aims to identify amniotic fluid (AF) protein biomarkers useful for the early diagnosis of PTB.

METHODS

We initially identified the protein expression profiles in the AF of women with PTB (n = 22) and full-term birth (FTB, n = 22), from the First People's Hospital of Yunnan Province who underwent amniocentesis from November 2019 to February 2020, using mass spectrometry employing the data-independent acquisition (DIA) technique, and then analyzed differentially expressed proteins (DEPs). Subsequently, the least absolute shrinkage and selection operator (LASSO) and random forest analysis were employed to further screen the key proteins for PTB biomarker identification. The receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analyses (DCA) were utilized to assess the discrimination and calibration of the key biomarkers.

RESULTS

A total of 25 DEPs were identified between the PTB and FTB groups, comprising 13 up-regulated and 12 down-regulated proteins. Three key protein biomarkers for early PTB diagnosis were identified: IL1RL1 (interleukin-1 receptor-like 1), APOE (apolipoprotein E), and NECTIN4 (nectin cell adhesion molecule 4). The results of the ROC analysis showed that the area under the curve (AUC) of the three proteins combined as a biomarker for early diagnosis of PTB was 0.913 (95% CI: 0.823-1.000), with a sensitivity of 0.864 and a specificity of 0.955, both superior to those of the individual biomarkers. Bootstrap internal validation revealed a concordance index (C-index) of 0.878, with a sensitivity of 0.812 and a specificity of 0.773, indicating the robust predictive performance of these biomarkers.

CONCLUSIONS

We identified three previously unexplored yet potentially useful protein biomarkers in AF for early PTB diagnosis: IL1RL1, APOE, and NECTIN4.

摘要

背景

尽管进行了广泛的研究，但识别有效的生物标志物以早期预测早产（PTB）仍然是一项具有挑战性的工作。本研究旨在确定用于早期诊断 PTB 的羊水（AF）蛋白生物标志物。

方法

我们最初使用非依赖性采集（DIA）技术通过质谱法鉴定了 2019 年 11 月至 2020 年 2 月期间在云南省第一人民医院接受羊膜穿刺术的 PTB（n=22）和足月分娩（FTB，n=22）女性的 AF 中的蛋白质表达谱，然后分析差异表达的蛋白质（DEPs）。随后，使用最小绝对收缩和选择算子（LASSO）和随机森林分析进一步筛选用于 PTB 生物标志物识别的关键蛋白。使用接收器工作特征（ROC）分析、校准图和决策曲线分析（DCA）评估关键生物标志物的区分度和校准度。

结果

PTB 组和 FTB 组之间共鉴定出 25 个 DEP，包括 13 个上调蛋白和 12 个下调蛋白。确定了三种用于早期 PTB 诊断的关键蛋白生物标志物：IL1RL1（白细胞介素 1 受体样 1）、APOE（载脂蛋白 E）和 NECTIN4（神经细胞粘附分子 4）。ROC 分析结果表明，这三种蛋白质组合作为早期诊断 PTB 的生物标志物的曲线下面积（AUC）为 0.913（95%CI：0.823-1.000），敏感性为 0.864，特异性为 0.955，均优于单个生物标志物。自举内部验证显示一致性指数（C-index）为 0.878，敏感性为 0.812，特异性为 0.773，表明这些生物标志物具有稳健的预测性能。