Department of Gynecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Zhejiang University School of Medicine First Affiliated Hospital, Zhejiang Province, PR China; Biomedical Big Data Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, PR China.
Mol Cell Proteomics. 2024 Nov;23(11):100848. doi: 10.1016/j.mcpro.2024.100848. Epub 2024 Sep 24.
Early pregnancy loss (EPL) is a common event in human reproduction and is classified into histological subtypes such as hydropic abortion (HA) and hydatidiform moles, including complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs). However, accurate diagnosis and improved patient management remain challenging due to high rates of misdiagnosis and diverse prognostic risks. Therefore, diagnostic biomarkers for EPL are urgently needed. Our study aimed to identify biomarkers for EPL through comprehensive proteomic analysis. Ten CHMs, six PHMs, ten HAs, and 10 normal control products of conception were used to obtain a proteomic portrait. Parallel reaction monitoring-targeted proteomic and regression analyses were used to verify and select the diagnostic signatures. Finally, 14 proteins were selected and a panel of diagnostic classifiers (DLK1, SPTB/COL21A1, and SAR1A) was built to represent the CHM, PHM, and normal control groups (area under the receiver operating characteristic curve = 0.900, 0.804/0.885, and 0.991, respectively). This high diagnostic power was further validated in another independent cohort (n = 148) by immunohistochemistry (n = 120) and Western blot analyses (n = 28). The protein SPTB was selected for further biological behavior experiments in vitro. Our data suggest that SPTB maintains trophoblast cell proliferation, angiogenesis, cell motility, and the cytoskeleton network. This study provides a comprehensive proteomic portrait and identifies potential diagnostic biomarkers. These findings enhance our understanding of EPL pathogenesis and offer novel targets for diagnosis and therapeutic interventions.
早期妊娠丢失（EPL）是人类生殖中的一种常见事件，可分为组织学亚型，如羊水过多性流产（HA）和葡萄胎，包括完全性葡萄胎（CHM）和部分性葡萄胎（PHM）。然而，由于误诊率高和预后风险多样化，准确的诊断和改善患者管理仍然具有挑战性。因此，迫切需要用于 EPL 的诊断生物标志物。我们的研究旨在通过全面的蛋白质组学分析来鉴定 EPL 的生物标志物。使用 10 例 CHM、6 例 PHM、10 例 HA 和 10 例正常妊娠产物获得蛋白质组图谱。平行反应监测靶向蛋白质组学和回归分析用于验证和选择诊断特征。最终选择了 14 种蛋白质，并构建了一个诊断分类器（DLK1、SPTB/COL21A1 和 SAR1A）的面板，以代表 CHM、PHM 和正常对照组（接受者操作特征曲线下面积分别为 0.900、0.804/0.885 和 0.991）。通过免疫组织化学（n=120）和 Western blot 分析（n=28）在另一个独立队列（n=148）中进一步验证了这种高诊断能力。选择蛋白质 SPTB 进行进一步的体外生物学行为实验。我们的数据表明，SPTB 维持滋养细胞增殖、血管生成、细胞迁移和细胞骨架网络。本研究提供了全面的蛋白质组图谱，并确定了潜在的诊断生物标志物。这些发现增强了我们对 EPL 发病机制的理解，并为诊断和治疗干预提供了新的靶点。
