Systematic Identification of Hub Genes in Placenta Accreta Spectrum Based on Integrated Transcriptomic and Proteomic Analysis.
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SUBMITTER: Chen B
PROVIDER: S-EPMC7522549 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Systematic Identification of Hub Genes in Placenta Accreta Spectrum Based on Integrated Transcriptomic and Proteomic Analysis.
Chen Bingnan B Wang Di D Bian Yue Y Li Jiapo J Yang Tian T Li Na N Qiao Chong C
Frontiers in genetics 20200915
Placenta accreta spectrum (PAS) is a pathological condition of the placenta with abnormal adhesion or invasion of the placental villi to the uterine wall, which is associated with a variety of adverse maternal and fetal outcomes. Although some PAS-related molecules have been reported, the underlying regulatory mechanism is still unclear. Compared with the study of single gene or pathway, omics study, using advanced sequencing technology and bioinformatics methods, can increase our systematic und ...[more]
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Project description:Placenta accreta spectrum (PAS) presents a significant obstetric challenge, associated with considerable maternal and fetal-neonatal morbidity and mortality. Nevertheless, it is imperative to acknowledge that a noteworthy subset of PAS cases remains undetected until the time of delivery, thereby contributing to an augmented incidence of morbidity among the affected individuals. The delayed identification of PAS not only hinders timely intervention but also exacerbates the associated health risks for both the maternal and fetal outcomes. This underscores the urgency to innovate strategies for early PAS diagnosis. In this study, we aimed to explore plasma proteins as potential diagnostic biomarkers for PAS. Integrated transcriptome and proteomic analyses were conducted to establish a novel diagnostic approach. A cohort of 15 pregnant women diagnosed with PAS and delivering at Inonu University Faculty of Medicine between 01/04/2021 and 01/01/2023, along with a matched control group of 15 pregnant women without PAS complications, were enrolled. Plasma protein identification utilized enzymatic digestion and liquid chromatography-tandem mass spectrometry techniques. Proteomic analysis identified 228 plasma proteins, of which 85 showed significant differences (P < 0.001) between PAS and control cases. We refined this to a set of 20 proteins for model construction, resulting in a highly accurate classification model (96.9% accuracy). Notable associations were observed for proteins encoded by P01859 (Immunoglobulin heavy constant gamma 2), P02538 (Keratin type II cytoskeletal 6A), P29622 [Kallistatin (also known as Serpin A4)], P17900 (Ganglioside GM2 activator Calmodulin-like protein 5), and P01619 (Immunoglobulin kappa variable 3-20), with fold changes indicating their relevance in distinguishing PAS from control groups. In conclusion, our study has identified novel plasma proteins that could serve as potential biomarkers for early diagnosis of PAS in pregnant women. Further research and validation in larger PAS cohorts are necessary to determine the clinical utility and reliability of these proteomic biomarkers for diagnosing PAS.
| S-EPMC10837117 | biostudies-literature
Project description:Atopic dermatitis (AD) is a severe inflammatory skin disorder, characterized by elevated levels of proinflammatory cytokines that fuel a vicious cycle of inflammation. While inflammatory recombinant human epidermal (RHE) models relevant to AD have been established, comprehensive understanding remains limited. To illuminate changes and identify potential hub genes involved in AD-related inflammation, RHE models, stimulated by an inflammatory cocktail including polyinosinic-polycytidylic acid, tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4) and interleukin 13 (IL-13), were constructed and examined using tandem mass tags-proteomic coupled with RNA-seq transcriptomic analyses. Principal component analysis (PCA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment were employed for the analysis of related genes and proteins. Protein-protein interaction networks helped identify hub genes, which were further confirmed by qPCR and western blot. We observed high expression of thymic stromal lymphopoietin in the inflammatory RHE. Our study identified 2369 differentially expressed genes and 880 differentially expressed proteins in the cocktail-induced group versus the normal control group. A total of 248 overlapping symbols were enriched in various biological processes and signaling pathways, including cornification envelope, cell-cell junction, calcium ion binding, extracellular matrix receptor, terpenoid backbone biosynthesis, and peroxisome proliferator-activated receptors signaling pathway, among others. Among the 248 overlapping symbols, CytoHubba identified 10 hub molecules, namely signal transducer and activator of transcription 3 (STAT3), integrin subunit beta 1 (ITGB1), filaggrin (FLG), involucrin (IVL), DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 (DDX58), small proline rich protein 1B (SPRR1B), interferon induced with helicase C domain 1 (IFIH1), desmoglein 1 (DSG1), collagen type XVII alpha 1 chain (COL17A1), and integrin subunit alpha 6 (ITGA6), based on the degree. These integrated results offer valuable insights into the molecular mechanisms of AD and present potential tools for screening cosmetic formulations intended for the treatment of AD.
| S-EPMC10787623 | biostudies-literature
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.
| S-EPMC10509122 | biostudies-literature
Project description:Placenta accreta spectrum (PAS) is characterized by abnormal attachment of the placenta to the uterus, and attempts at placental delivery can lead to catastrophic maternal hemorrhage and death. Multidisciplinary delivery planning can significantly improve outcomes; however, current diagnostics are lacking as approximately half of pregnancies with PAS are undiagnosed prior to delivery. This is a nested case-control study of 35 cases and 70 controls with the primary objective of identifying circulating microparticle (CMP) protein panels that identify pregnancies complicated by PAS. Size exclusion chromatography and liquid chromatography with tandem mass spectrometry were used for CMP protein isolation and identification, respectively. A two-step iterative workflow was used to establish putative panels. Using plasma sampled at a median of 26 weeks' gestation, five CMP proteins distinguished PAS from controls with a mean area under the curve (AUC) of 0.83. For a separate sample taken at a median of 35 weeks' gestation, the mean AUC was 0.78. In the second trimester, canonical pathway analyses demonstrate over-representation of processes related to iron homeostasis and erythropoietin signaling. In the third trimester, these analyses revealed abnormal immune function. CMP proteins classify PAS well prior to delivery and have potential to significantly reduce maternal morbidity and mortality.
| S-EPMC9814521 | biostudies-literature
Project description:BackgroundUterine 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 descriptionA 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.ConclusionsWith 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.
| S-EPMC9929783 | biostudies-literature
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.
| S-EPMC9396360 | biostudies-literature
Project description:Objective: To evaluate the use of tourniquet and forceps to reduce bleeding during surgical treatment of severe placenta accreta spectrum (placenta increta and placenta percreta). Methods: A tourniquet was used in the lower part of the uterus during surgical treatment of severe placenta accreta spectrum. Severe placenta accreta spectrum was classified into two types according to the relative position of the placenta and tourniquet during surgery: upper-tourniquet type, in which the entire placenta was above the tourniquet, and lower-tourniquet type, in which part or all of the placenta was below the tourniquet. The surgical effects of the two types were retrospectively compared. We then added forceps to the lower-tourniquet group to achieve further bleeding reduction. Finally, the surgical effects of the two types were prospectively compared. Results: During the retrospective phase, patients in the lower-tourniquet group experienced more severe symptoms than did patients in the upper-tourniquet group, based on mean intraoperative blood loss (upper-tourniquet group 787.5 ml, lower-tourniquet group 1434.4 ml) intensive care unit admission rate (upper-tourniquet group 1.0%, lower-tourniquet group 33.3%), and length of hospital stay (upper-tourniquet group 10.2d, lower-tourniquet group 12.1d). During the prospective phase, after introduction of the revised surgical method involving forceps (in the lower-tourniquet group), the lower-tourniquet group exhibited improvements in the above indicators (intraoperative average blood loss 722.9 ml, intensive care unit admission rate 4.3%, hospital stays 9.0d). No increase in the rate of complications was observed. Conclusion: The relative positions of the placenta and tourniquet may influence the perioperative risk of severe placenta accreta spectrum. The method using a tourniquet (and forceps if necessary) can improve the surgical effect in cases of severe placenta accreta spectrum.
| S-EPMC8558214 | biostudies-literature
Project description:Objective To examine the association between conservative treatment for PAS (placenta accreta spectrum) and subsequent gynecological and fertility complications. Methods All women who underwent conservative treatment for PAS between January 1990 and December 2000 were included in this retrospective cohort study conducted in a tertiary teaching hospital. Gynecological and fertility complications experienced after the index delivery were collected from the medical records and telephone questionnaires. This data was compared to an age and parity-matched control group of women without PAS. Results The study group included 134 women with PAS managed conservatively and 134 controls with normal deliveries matched by parity and age. Women in the PAS group required significantly more postpartum operative procedures such as hysteroscopy or D&C (OR = 6.6; 95%CI: 3.36–13.28; P = <0.001). Following the index delivery, there were 345 pregnancies among 107 women who attempted conception following conservative treatment for PAS vs. 339 pregnancies among 105 women who attempted conception in the control group. Among women who attempted conception following conservative treatment for PAS 99 (92.5%) delivered live newborns (a total of 280 deliveries) vs. 94 (89.5%) in the control group, (a total of 270 live newborns, p = 0.21). The need for fertility treatments was not different between the two groups (OR = 1.22; 95%CI: 0.51–2.93; P = 0.66). Conclusion After conservative treatment for PAS, significantly more women required complementary procedures due to retained placenta and/or heavy vaginal bleeding. There was no evidence of fertility impairment in women post-conservative treatment for PAS.
| S-EPMC9650034 | biostudies-literature
Project description:BackgroundOn a global scale, cases of placenta accreta spectrum are often just identified during cesarean delivery because they are missed during antenatal care screening. Routine operating teams not trained in the management of placenta accreta spectrum are faced with difficult surgical situations and have to make decisions that may define the clinical outcomes. Although there are general recommendations for the intraoperative management of placenta accreta spectrum, no studies have described the clinical reality of unexpected placenta accreta spectrum cases in resource-poor settings.ObjectiveThis study aimed to describe the maternal outcomes of previously undiagnosed placenta accreta spectrum managed in resource-poor settings in Colombia and Indonesia.Study designThis was a retrospective case series of women with histologically confirmed placenta accreta spectrum treated in 2 placenta accreta spectrum centers after referral from remote resource-poor hospitals. Clinical outcomes were analyzed according to the initial type of management: (1) no cesarean delivery; (2) placenta left in situ after cesarean delivery; (3) partial removal of the placenta after cesarean delivery; and (4) post-cesarean hysterectomy. In addition, we evaluated the use of telemedicine by comparing the outcomes of women in hospitals that used the support of the placenta accreta spectrum center during the initial surgery.ResultsA total of 29 women who were initially managed in Colombia (n=2) and Indonesia (n=27) were included. The lowest volume of blood loss and the lowest frequency of complications were in women who underwent deferred cesarean delivery (n=5; 17.2%) and in those who had a delayed placental delivery (n=5; 20.7%). Five maternal deaths (14%) occurred in the group that did not receive telehelp, and 4 women died of irreversible shock because of uncontrolled bleeding.ConclusionPreviously undiagnosed placenta accreta spectrum in resource-poor hospitals was associated with a high risk of maternal mortality. Open-close abdominal surgery or leaving the placenta in situ seem to be the best choices for unexpected placenta accreta spectrum management in resource-poor settings. Telemedicine with a placenta accreta spectrum center may improve prognosis.
| S-EPMC10165260 | biostudies-literature
Project description:BackgroundPlacenta 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.MethodsUsing 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.ResultsUpon 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.ConclusionsWe identified a ceRNA regulatory mechanism in PAS, and two miRNAs that may potentially serve as biomarkers of PAS prognosis.
| S-EPMC7475428 | biostudies-literature