Integrative multi-omic analysis reveals potential biomarkers in the cervicovaginal fluid of patients with placenta accrete spectrum.

IF 2.8 2区 医学 Q1 OBSTETRICS & GYNECOLOGY
Hai Jiang, Jiangxue Qu, Nana Huang, Zeli Li, Xiaoming Shi, Lian Chen, Yangyu Zhao
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Abstract

Objective: This study aimed to detect the proteins and metabolites in the cervicovaginal fluid to observe their relationship with the occurrence of placenta accreta spectrum and the potential biomarkers with predictive value.

Methods: Cervicovaginal fluid samples were collected before delivery from 6 participants of PAS and 6 controls subjects with similar gestational ages. The severity of PAS was evaluated by ultrasound and MRI scoring system and confirmed by the intraoperative findings or pathological examination. We used 4D label-free quantitative proteomics and untargeted metabolomics to identify the proteins and metabolites in cervicovaginal fluid, and analyzed the functions of differential expressed proteins or metabolites in PAS by multi-omics combined with bioinformatics analysis.

Results: Proteomics and metabolomics screened 127 and 12 differential expressed proteins and metabolites in CVF of PAS, respectively. Proteins and metabolites that significantly dysregulated in participants with placenta accreta spectrum were factors that regulate angiogenesis, and extracellular matrix proteins that regulate trophoblast invasion. Among them, the important difference expressed proteins/metabolites with representative significance are arginine, GAL7, uPA, MMP9 and ITGAM, that may be useful as potential biomarkers for the prediction and early diagnosis of PAS.

Conclusion: Cervicovaginal fluid in patients with PAS presents a protein-metabolic microenvironment that promotes trophoblast invasion, endothelial activation and vascular proliferation.

综合多组学分析揭示了胎盘增生患者宫颈阴道液中潜在的生物标志物。
目的:本研究旨在检测宫颈阴道液中蛋白质及代谢物,观察其与胎盘增生发生的关系及潜在的具有预测价值的生物标志物。方法:对6例妊高征患者和6例胎龄相近的对照组进行产前宫颈阴道液采集。通过超声和MRI评分系统评估PAS的严重程度,并通过术中表现或病理检查证实。我们采用4D无标记定量蛋白质组学和非靶向代谢组学对宫颈阴道液中的蛋白质和代谢物进行鉴定,并采用多组学结合生物信息学分析的方法分析PAS中差异表达蛋白或代谢物的功能。结果:蛋白质组学和代谢组学分别筛选到PAS CVF中127个和12个差异表达蛋白和代谢物。在胎盘增生谱的参与者中,蛋白质和代谢物的显著失调是调节血管生成的因素,以及调节滋养细胞侵袭的细胞外基质蛋白。其中,具有代表意义的重要差异表达蛋白/代谢物为精氨酸、GAL7、uPA、MMP9和ITGAM,可能作为潜在的生物标志物用于PAS的预测和早期诊断。结论:PAS患者的宫颈阴道液呈现蛋白质代谢微环境,促进滋养细胞侵袭、内皮细胞活化和血管增殖。
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来源期刊
BMC Pregnancy and Childbirth
BMC Pregnancy and Childbirth OBSTETRICS & GYNECOLOGY-
CiteScore
4.90
自引率
6.50%
发文量
845
审稿时长
3-8 weeks
期刊介绍: BMC Pregnancy & Childbirth is an open access, peer-reviewed journal that considers articles on all aspects of pregnancy and childbirth. The journal welcomes submissions on the biomedical aspects of pregnancy, breastfeeding, labor, maternal health, maternity care, trends and sociological aspects of pregnancy and childbirth.
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