Dataset Information

Development and validation of a four-microRNA signature for placenta accreta spectrum: an integrated competing endogenous RNA network analysis.

ABSTRACT:

Background

Placenta accreta spectrum (PAS) is a major cause of maternal morbidity and mortality in modern obstetrics, however, few studies have explored the underlying molecular mechanisms and biomarkers. In this study, we aimed to elucidate the regulatory RNA network contributing to PAS, comprising long non-coding (lnc), micro (mi), and messenger (m) RNAs, and identify biomarkers for the prediction of intraoperative blood volume loss.

Methods

Using RNA sequencing, we compared mRNA, lncRNA, and miRNA expression profiles between five PAS and five normal placental tissues. Furthermore, the miRNA expression profiles in maternal plasma samples from ten PAS and ten control participants were assessed. The data and clinical information were analyzed using R language and GraphPad Prism 7 software.

Results

Upon comparing PAS and control placentas, we identified 8,806 lncRNAs, 128 miRNAs, and 1,788 mRNAs that were differentially expressed. Based on a lasso regression analysis and correlation predictions, we developed a competing endogenous (ce) RNA network comprising 20 lncRNAs, 4 miRNAs, and 19 mRNAs. This network implicated a reduced angiogenesis pathway in PAS, and correlation analyses indicated that two miRNAs (hsa-miR-490-3p and hsa-miR-133a-3p) were positively correlated to operation-related blood volume loss.

Conclusions

We identified a ceRNA regulatory mechanism in PAS, and two miRNAs that may potentially serve as biomarkers of PAS prognosis.

SUBMITTER: Yang T

PROVIDER: S-EPMC7475428 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Development and validation of a four-microRNA signature for placenta accreta spectrum: an integrated competing endogenous RNA network analysis.

Yang Tian T Li Na N Hou Rui R Qiao Chong C Liu Caixia C

Annals of translational medicine 20200801 15

<h4>Background</h4>Placenta accreta spectrum (PAS) is a major cause of maternal morbidity and mortality in modern obstetrics, however, few studies have explored the underlying molecular mechanisms and biomarkers. In this study, we aimed to elucidate the regulatory RNA network contributing to PAS, comprising long non-coding (lnc), micro (mi), and messenger (m) RNAs, and identify biomarkers for the prediction of intraoperative blood volume loss.<h4>Methods</h4>Using RNA sequencing, we compared mRN ...[more]

PMID: 32953719

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Project description:BackgroundPlacenta accreta spectrum disorders are a complex range of placental pathologies that are associated with significant maternal morbidity and mortality. A diagnosis of placenta accreta spectrum relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNAs are small RNA molecules that reflect the cellular processes of the origin tissues.ObjectiveWe aimed to explore exosomal microRNA expression to understand placenta accreta spectrum pathology and clinical use for placenta accreta spectrum detection.Study designThis study was a biomarker analysis of prospectively collected samples at 2 academic institutions from 2011 to 2022. Plasma specimens were collected from patients with suspected placenta accreta spectrum, placenta previa, or repeat cesarean deliveries. Exosomes were quantified and characterized by nanoparticle tracking analysis and western blotting. MicroRNA were assessed by polymerase chain reaction array and targeted single quantification. MicroRNA pathway analysis was performed using the Ingenuity Pathway Analyses software. Placental biopsies were taken from all groups and analyzed by polymerase chain reaction and whole cell enzyme-linked immunosorbent assay. Receiver operating characteristic curve univariate analysis was performed for the use of microRNA in the prediction of placenta accreta spectrum. Clinically relevant outcomes were collected from abstracted medical records.ResultsPlasma specimens were analyzed from a total of 120 subjects (60 placenta accreta spectrum, 30 placenta previa, and 30 control). Isolated plasma exosomes had a mean size of 71.5 nm and were 10 times greater in placenta accreta spectrum specimens (20 vs 2 particles/frame). Protein expression of exosomes was positive for intracellular adhesion molecule 1, flotilin, annexin, and CD9. MicroRNA analysis showed increased detection of 3 microRNAs (mir-92, -103, and -192) in patients with placenta accreta spectrum. Pathway interaction assessment revealed differential regulation of p53 signaling in placenta accreta spectrum and of erythroblastic oncogene B2 or human epidermal growth factor 2 in control specimens. These findings were subsequently confirmed in placental protein analysis. Placental microRNA paralleled plasma exosomal microRNA expression. Biomarker assessment of placenta accreta spectrum signature microRNA had an area under the receiver operating characteristic curve of 0.81 (P<.001; 95% confidence interval, 0.73-0.89) with a sensitivity and specificity of 89.2% and 80%, respectively.ConclusionIn this large cohort, plasma exosomal microRNA assessment revealed differentially expressed pathways in placenta accreta spectrum, and these microRNAs are potential biomarkers for the detection of placenta accreta spectrum.

Project description:BackgroundPlacenta accreta spectrum (PAS) is a rare, life-threatening complication of pregnancy. Predicting PAS severity is critical to individualise care planning for the birth. We aim to explore whether radiomic analysis of T2-weighted magnetic resonance imaging (MRI) can predict severe cases by distinguishing between histopathological subtypes antenatally.MethodsThis was a bi-centre retrospective analysis of a prospective cohort study conducted between 2018 and 2022. Women who underwent MRI during pregnancy and had histological confirmation of PAS were included. Radiomic features were extracted from T2-weighted images. Univariate regression and multivariate analyses were performed to build predictive models to differentiate between non-invasive (International Federation of Gynecology and Obstetrics [FIGO] grade 1 or 2) and invasive (FIGO grade 3) PAS using R software. Prediction performance was assessed based on several metrics including sensitivity, specificity, accuracy and area under the curve (AUC) at receiver operating characteristic analysis.ResultsForty-one women met the inclusion criteria. At univariate analysis, 0.64 sensitivity (95% confidence interval [CI] 0.0-1.00), specificity 0.93 (0.38-1.0), 0.58 accuracy (0.37-0.78) and 0.77 AUC (0.56-.097) was achieved for predicting severe FIGO grade 3 PAS. Using a multivariate approach, a support vector machine model yielded 0.30 sensitivity (95% CI 0.18-1.0]), 0.74 specificity (0.38-1.00), 0.58 accuracy (0.40-0.82), and 0.53 AUC (0.40-0.85).ConclusionOur results demonstrate a predictive potential of this machine learning pipeline for classifying severe PAS cases.Relevance statementThis study demonstrates the potential use of radiomics from MR images to identify severe cases of placenta accreta spectrum antenatally.Key points• Identifying severe cases of placenta accreta spectrum from imaging is challenging. • We present a methodological approach for radiomics-based prediction of placenta accreta. • We report certain radiomic features are able to predict severe PAS subtypes. • Identifying severe PAS subtypes ensures safe and individualised care planning for birth.

Project description:Background Uterine incarceration is a rare obstetric complication that is always associated with retroversion and prone to misdiagnosis. Pelvic examination and imaging methods including ultrasound and magnetic resonance imaging (MRI) are used as the primary diagnostic tool. We present an asymptomatic anterior uterine incarceration complicated by placenta previa and placenta accreta spectrum (PAS) disorder, which could be diagnosed during the pregnancy periods, but was first diagnosed during the cesarean section (CS) and got the surgeons into trouble. Case Description A 28-year-old woman, gravidity 4, parity 1, was hospitalized due to placenta previa and PAS disorder diagnosed by ultrasound and MRI at 35.6 weeks of gestation. She had not experienced any discomfort. Given her history of a previous CS, she underwent a well-prepared cesarean delivery for the termination of the pregnancy. The patient had a series of periodical ultrasound and MRI examinations in which placenta previa and placenta accreta were described in disregard of the abnormal location of cervix; consequently, interior uterine incarceration was first diagnosed during the surgery, which caused significant difficulties in the operation which lasted 3 hours and 21 minutes. The patient developed severe hemorrhaging and lost approximately 5,000 mL of blood. Fortunately, she delivered a health male infant weighing 3,440 grams with quite good Apgar scores. During the follow-up, maternal and child health was confirmed. Conclusions With regard to patients who have undergone previous pelvic surgery, doctors need to pay close attention to the position of the cervix, the pelvic adhesion situation during the prenatal examination, and be on alert for uterine incarceration. Uterine incarceration can be accurately recognized by periodic sonography and MRI if the radiologist is aware of this unusual condition. We do suggest that special are must be taken to avoid unnecessary trauma by misdiagnosis because of lack of awareness.

Project description:ImportancePlacenta previa is widely acknowledged as a risk factor for placenta accreta spectrum (PAS) disorders, which are severe maternal complications; however, data are limited regarding whether placenta previa is associated with a higher risk of worse maternal outcomes among patients with PAS disorders.ObjectiveTo examine the association between placenta previa and the risk of severe maternal morbidities (SMMs) and higher resource use among patients with PAS disorders.Design, setting, and participantsThis retrospective cohort study extracted records of 3793 patients with PAS diagnosis and delivery indicators between October 1, 2015, and December 31, 2019, from the US National Inpatient Sample database.ExposuresPlacenta previa.Main outcomes and measuresData on 21 Centers for Disease Control and Prevention-defined SMMs and 25 study-defined surgical morbidities associated with PAS were extracted. Six surgical procedures (cystoscopy, intra-arterial balloon occlusion, cesarean delivery, hysterectomy, cystectomy, and oophorectomy), hospital length of stay, and inpatient costs were compared. Multivariable Poisson regression models built in the generalized estimating equation framework were used.ResultsAmong 3793 patients with PAS (median [IQR] age at admission, 33 [29-37] years), 621 women (16.4%) were Black, 765 (20.2%) were Hispanic, 1779 (46.9%) were White, 441 (11.6%) were of other races and/or ethnicities (47 [1.2%] were American Indian, 220 [5.8%] were Asian or Pacific Islander, and 174 [4.6%] were of multiple or other races and/or ethnicities), and 187 (4.9%) were of unknown race and ethnicity. A total of 1323 patients (34.9%) had placenta previa and 2470 patients (65.1%) did not; of those with placenta previa, 405 patients (30.6%) had invasive PAS. Patients with vs without placenta previa had a significantly higher rate and risk of any SMM (935 women [70.7%] vs 1087 women [44.0%]; P < .001; adjusted risk ratio [aRR], 1.19; 95% CI, 1.12-1.27) and any surgical morbidity (1170 women [88.4%] vs 1667 women [67.5%]; P < .001; aRR, 1.18; 95% CI, 1.13-1.23). With regard to specific outcomes, those with vs without placenta previa had a significantly higher rate of peripartum hemorrhage (878 patients [66.4%] vs 1217 patients [49.3%]; P < .001), blood product transfusion (413 patients [31.2%] vs 610 patients [24.7%]; P < .001), shock (83 patients [6.3%] vs 108 patients [4.4%]; P = .01), disseminated intravascular coagulation or other coagulopathy (77 patients [5.8%] vs 105 patients [4.3%]; P = .04), and urinary tract injury (44 patients [3.3%] vs 41 patients [1.7%]; P = .002). Patients with vs without placenta previa were more likely to undergo cesarean delivery (1292 patients [97.7%] vs 1787 patients [72.3%]; P < .001), hysterectomy (786 patients [59.4%] vs 689 patients [27.9%]; P < .001), cystoscopy (301 patients [22.8%] vs 203 patients [8.2%]; P < .001), cystectomy (157 patients [11.9%] vs 98 patients [4.0%]; P < .001), and intra-arterial balloon occlusion (121 patients [9.1%] vs 77 patients [3.1%]; P < .001) and to have significantly longer hospital length of stay (median [IQR], 5 [4-11] days vs 3 [3-5] days; P < .001) and total inpatient costs (median [IQR], $17 496 [$10 863-$30 619] vs $9728 [$6130-$16 790]; P < .001). Hypertensive disorder of pregnancy was associated with a decreased risk of placenta previa (aRR, 0.67; 95% CI, 0.46-0.96) among patients with PAS.Conclusions and relevanceIn this study, placenta previa was associated with an increased risk of maternal and surgical morbidities and higher resource use among women with PAS. These findings suggest that interventions to alleviate maternal and surgical morbidities are especially needed for patients with placenta previa-complicated PAS disorders.

Dataset Information

Development and validation of a four-microRNA signature for placenta accreta spectrum: an integrated competing endogenous RNA network analysis.

Background

Methods

Results

Conclusions

Publications

Development and validation of a four-microRNA signature for placenta accreta spectrum: an integrated competing endogenous RNA network analysis.

Similar Datasets

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