ISSN Print 2500–1094
ISSN Online 2542–1204
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
ORIGINAL RESEARCH
Emerging prediction of preeclampsia based on the expression of exosomal SUMO proteins
About authors
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
Correspondence should be addressed: Vladoslava A. Gusar
Akademika Oparina, 4, Moscow, 117997, Russia; ur.liam@rasug_v
About paper
Funding: the study was supported by the RSF grant [22-15-00363 “Epigenetic and biochemical aspects of abnormal pregnancy in disturbances of the trophoblast invasive properties: from early diagnosis to prevention of maternal and perinatal morbidity”].
Author contribution: Gusar VA, Timofeeva AV — study concept; Fedorov IS — statistical analysis, graphic design; Gusar VA, Tarasova AM — research procedure (western blotting); Sukhova YuV, Ivanets TYu — providing the clinical basis, assessment of hormones; Gusar VA — data analysis/interpretation, manuscript writing; Timofeeva AV — editing.
Compliance with ethical standards: the study was approved by the Ethics Committee of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology (protocol № 13 dated 12 October 2015); the informed consent was obtained from all the patients enrolled.
Received: 2024-01-29
Accepted: 2024-02-20
Published online: 2024-02-29
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Fig. 1. Flowchart of the study population
Fig. 2. Western blot of membrane with conjugated exosomal forms of SUMO 1 (A), SUMO 2/3/4 (B), UBC9 (C) and hnRNPA2/B1 (D) in pregnant women with subsequently developed early-onset PE (EPE), late-onset PE (LPE), and physiological pregnancy (PP)
Fig. 3. Comparative analysis of SUMO 1 (A), SUMO 2/3/4 (B), UBC9 (C) and hnRNPA2/B1 (D) expression in exosomes in pregnant women with physiological pregnancy (PP), who subsequently developed early-onset PE (EPE), late-onset PE (LPE), and high risk of PE (HRPE). Total densitometry of proteins was quantified and normalized to loading control sample. Data presented in the format Me (Q1; Q3); *: significance level p ≤ 0.05 when compared with PP
Fig. 4. Comparative analysis of SUMO 1 (A), SUMO 2/3/4 (B), UBC9 (C) and hnRNPA2/B1 (D) expression in placental tissue in pregnant women with early-onset (EPE) and late-onset (LPE) PE, and age-matched controls (N < 34, N > 34). Total densitometry of proteins was quantified and normalized to loading control actin. Data presented in the format Me (Q1; Q3); *: significance level p ≤ 0,05 ≤ 0.05 when compared with age-matched controls
Fig. 5. ROC curves for a logistic model for the risk assessment of РЕ at early gestation by SUMO 1–4, UBC9 and hnRNPA2/B1 expression in exosomes (A–D). EPE is early-onset PE; LPE is late-onset PE; HRPE is high risk of PE; PP is physiological pregnancy
Table 1. The clinical characteristics of pregnant women (cohort I)
Note: EPE is early-onset preeclampsia; LPE is late-onset preeclampsia; PP is physiological pregnancy; PlGF is a placental growth factor; sFLT-1 is a soluble Fms-like tyrosine kinase 1; РАРР-А is a pregnancy-associated protein A; b-HCG is a human chorionic gonadotropin, subunit b; CRL is a crown-to-rump length; NTS is a nuchal translucency scan; PI UtA is a Pulsatility Index of the uterine artery; PI DV is a Pulsatility Index of ductus venosus; IP is an intrauterine pneumonia; IVH is an intraventricular hemorrhage; RDS is a respiratory distress syndrome; The median (Me) and quartiles Q1, Q3 in the format Me (Q1–Q3) were used in the case of non-normal distribution.
Table 2. The clinical characteristics of pregnant women (cohort II)
Note: EPE is early-onset preeclampsia; LPE is late-onset preeclampsia; NA here means “not analyzed”; VLBW is very low birth weight; The median (Me) and quartiles Q1, Q3 in the format Me (Q1 –Q3 ) were used in the case of non-normal distribution.
Table 3. The results of a correlation of protein expression in exosomes with indices of combined prenatal screening of pregnant women with early-onset and late-onset PE
Note: * r is a Spearman rank correlation coefficient; * * p is the statistical significance of correlation; Ns is not statistically significant.
Table 4. Predictive values with parameters of logistic models for SUMO 1–4, UBC9 and hnRNPA2/B1
Note: EPE is early-onset PE; LPE is late-onset PE; HRPE is high risk of PE; PP is physiological pregnancy; AUC is area under curve
