Comprehensive Proteomic Analysis Reveals Distinct Features and a Diagnostic Biomarker Panel for Early Pregnancy Loss in Histological Subtypes

• DOI: 10.1016/j.mcpro.2024.100848
• Publication Date: 2024-09-24T02:01:51Z
• Authors: Yating Zhao; Yingjiqiong Liang; Luya Cai; Limeng Cai; Bo Huang; Peilin Han; Xiaofei Zhang; Huifang Zhang; Zhen Chen; Xiangang Yin; Ping Duan; Huafeng Shou; Xiaoxu Zhu; Zhe Wang; Qihong Wan; Jinyan Huang; Jianhua Qian
• Keywords: 0301 basic medicine; 03 medical and health sciences; Research

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 (HMs), 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 ten normal control (NC) products of conception (POC) were used to obtain a proteomic portrait. Parallel reaction monitoring (PRM)-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 NC groups (auROC=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 (IHC) (n = 120) and western blot (WB) analyses (n = 28). The protein SPTB was selected for further biological behaviour 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.