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血清蛋白质组学鉴定基于超声心动图诊断的门肺高压的生物标志物和发病机制。

Serum proteomics identify biomarkers and pathogenesis of portopulmonary hypertension diagnosed based on echocardiography.

作者信息

Du Jialin, Zhang Yifu, Hao Diandian, Wang Hui, Ren Yulin, Song Yuze, Wen Xiaoyu

机构信息

Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun, 130021, China.

Meihekou Central Hospital, Meihekou, 135022, China.

出版信息

Sci Rep. 2025 Jul 1;15(1):21075. doi: 10.1038/s41598-025-08376-6.

Abstract

Portal pulmonary hypertension (PoPH), a severe complication of portal hypertension (PHTN), is marked by elevated pulmonary arterial pressure, but its pathophysiological mechanisms are unclear. This study used proteomics to identify differentially expressed proteins (DEPs) and genes in Patients with PoPH compared to those with PHTN and healthy controls (HC), aiming to uncover potential biomarkers for diagnosis and treatment. Patients with liver cirrhosis and PHTN, admitted between January 2023 and May 2024, were classified into PoPH and non-PoPH (PHTN) groups based on echocardiography. Serum from 12 PoPH, 12 PHTN, and 6 HC was analyzed using data-independent acquisition (DIA) proteomics to identify DEPs. Protein-protein interaction (PPI) networks identified key DEPs, and ELISA was performed for biomarker validation. Compared to HC, 374 proteins were upregulated and 115 downregulated in PoPH, while 18 were upregulated and 38 downregulated in PHTN. KEGG and GO analyses linked DEPs to immune response, metabolism, and cell signaling. Thirty-five proteins distinguish PoPH from HC and PHTN. Vitronectin (VTN, P04004) was correlated with RDW (R = -0.56, P < 0.01) and PLT (R = 0.52, P < 0.01). ELISA confirmed lower VTN levels in PoPH (P < 0.05). This study identified 35 serum proteins involved in PoPH, with VTN as a potential biomarker for distinguishing PoPH from PHTN and HC. Further research is needed to explore these findings.

摘要

门脉性肺动脉高压(PoPH)是门静脉高压(PHTN)的一种严重并发症,其特征为肺动脉压升高,但其病理生理机制尚不清楚。本研究采用蛋白质组学方法,鉴定PoPH患者与PHTN患者及健康对照(HC)相比差异表达的蛋白质(DEP)和基因,旨在发现潜在的诊断和治疗生物标志物。2023年1月至2024年5月收治的肝硬化和PHTN患者,根据超声心动图分为PoPH组和非PoPH(PHTN)组。使用数据非依赖采集(DIA)蛋白质组学分析12例PoPH患者、12例PHTN患者和6例HC的血清,以鉴定DEP。蛋白质-蛋白质相互作用(PPI)网络确定关键DEP,并进行酶联免疫吸附测定(ELISA)以验证生物标志物。与HC相比,PoPH中有374种蛋白质上调,115种下调,而PHTN中有18种上调,38种下调。京都基因与基因组百科全书(KEGG)和基因本体(GO)分析将DEP与免疫反应、代谢和细胞信号传导联系起来。35种蛋白质可区分PoPH与HC和PHTN。玻连蛋白(VTN,P04004)与红细胞分布宽度(RDW,R = -0.56,P < 0.01)和血小板(PLT,R = 0.52,P < 0.01)相关。ELISA证实PoPH中VTN水平较低(P < 0.05)。本研究鉴定出35种参与PoPH的血清蛋白,其中VTN是区分PoPH与PHTN和HC的潜在生物标志物。需要进一步研究以探索这些发现。

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