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Ultrasound in Obstetrics & Gynecology :... Jun 2019Fetal aberrant right subclavian artery (ARSA) is a relatively common sonographic finding. Several studies have reported a significant association between ARSA and Down...
OBJECTIVES
Fetal aberrant right subclavian artery (ARSA) is a relatively common sonographic finding. Several studies have reported a significant association between ARSA and Down syndrome, as well as 22q11.2 microdeletion. The objective of this study was to assess the risk of abnormal chromosomal microarray analysis (CMA) findings in a large cohort of pregnancies with fetal ARSA as an isolated, as well as a non-isolated, sonographic anomaly. A secondary objective was to review the literature, examining the frequency of chromosomal microarray aberrations in fetuses with isolated ARSA.
METHODS
Data from all pregnancies referred for invasive testing and CMA due to sonographic diagnosis of fetal ARSA, between 2013 and 2017, were obtained retrospectively from the computerized database of the Israeli Ministry of Health. The rate of clinically significant CMA findings in these fetuses was compared to that in a local control population of 2752 low-risk pregnancies with normal ultrasound and serum screening results. In addition, a literature search was conducted in PubMed, from inception to February 2018, of original studies in the English language describing the frequency and nature of microscopic and submicroscopic aberrations in fetuses with isolated ARSA.
RESULTS
Of 246 pregnancies with isolated ARSA that underwent CMA analysis, a clinically significant finding was detected in one (0.4%) pregnancy (trisomy 21). This rate did not differ significantly from that in the control population (P = 0.1574). Of 22 fetuses with non-isolated ARSA, one (4.5%) additional case of trisomy 21 was noted. The frequency of trisomy 21 in this cohort also did not differ from that in the control population (relative risk, 5.5 (95% CI, 0.8-37.6)). The literature search yielded 13 additional relevant papers, encompassing 333 cases of isolated ARSA. Of 579 cases overall (including those of the present study), 13 (2.2%) cases of trisomy 21 were detected, with no cases of 22q11.2 microdeletion.
CONCLUSION
While an association may exist between non-isolated ARSA and Down syndrome, isolated ARSA might better serve as a soft marker for Down syndrome, rather than a routine indication for invasive prenatal testing. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Cardiovascular Abnormalities; Cohort Studies; Down Syndrome; Female; Humans; Israel; Microarray Analysis; Pregnancy; Subclavian Artery; Ultrasonography, Prenatal
PubMed: 30584678
DOI: 10.1002/uog.20208 -
International Journal of Surgery... Jan 2020Advanced colorectal has poor survival and are difficult to treat. Therefore, there is an urgent need for biomarkers to diagnose this cancer at earlier manageable stages.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Advanced colorectal has poor survival and are difficult to treat. Therefore, there is an urgent need for biomarkers to diagnose this cancer at earlier manageable stages. Micro-RNAs (miRNAs) are amongst the most significant biomarkers that have shown promise in improving management and early detection of different types of cancers. However, since MiRNAs are non-coding, the main limitation of using them as biomarkers is that they do not have associated phenotype and therefore difficult to validate using other techniques. This makes it difficult to understand the mechanism of miRNA is disease initiation and progression, therefore any methodology that can provide semantics to miRNA expression would enhance the understanding of the role of miRNA in disease.
METHODS
Here we report an integrative meta-analysis and bioinformatics methodology that showed microRNA-21 and its associated target mRNA to be the most significant predictive biomarkers for colorectal adenoma and adenocarcinoma. After drawing key inferences by meta-analysis, the authors then developed a bioinformatics method to identify mir-21 gene targeting in a specific tissue using two different bioinformatics approaches; absolute GSEA (Gene Set Enrichment Analysis) and LIMMA (Linear Models for MicroArray data) to identify differentially expressed genes of miRNA-21.
RESULTS
Results from GSEA intersection with mir-21 gene targets was a subset of longer gene list that was obtained from the GEO2R intersect. In our study, both of longer GEO2R gene target list and the more focused GSEA list established the fact that mir-21 target numerous functional pathways that are mostly interconnected. Our three steps bioinformatics approach identified ABCB1, HPGD, BCL2, TIAM1, TLR3, and PDCD4 as common targets for mir-21 in both of adenoma as well as adenocarcinoma suggesting they are biomarkers for early CRC.
CONCLUSIONS
The approach in this study proposed combining the big data from the scientific literature together with novel bioinformatics to bring about a methodology that can be used to first identify which microRNAs are involved in a specific disease, and then to identify a panel of biomarkers derived from the microRNAs target genes, and from these target genes the functional significance of these microRNAs can be inferred providing better clinical value for the surgeon.
Topics: Adenocarcinoma; Adenoma; Apoptosis Regulatory Proteins; Biomarkers, Tumor; Colorectal Neoplasms; Computational Biology; Early Detection of Cancer; Humans; MicroRNAs; RNA-Binding Proteins
PubMed: 31756546
DOI: 10.1016/j.ijsu.2019.11.017 -
BJOG : An International Journal of... Nov 2023Brain anomalies (BAs) have been the focus of research, as they have a high impact on fetal health but therapeutic and diagnostic approaches are limited. (Review)
Review
Diagnostic yield of prenatal exome sequencing in the genetic screening of fetuses with brain anomalies detected by MRI and ultrasonography: A systematic review and meta-analysis.
BACKGROUND
Brain anomalies (BAs) have been the focus of research, as they have a high impact on fetal health but therapeutic and diagnostic approaches are limited.
OBJECTIVES
In this study, the application and efficiency of exome sequencing (ES) in detecting different cases of BAs in fetuses were evaluated and compared with chromosomal microarray analysis (CMA).
SEARCH STRATEGY
To conduct this study, three databases including PubMed, Web of Science and Embase were utilised with the keywords 'prenatal', 'diagnoses', 'brain anomalies' and 'exome sequencing'.
SELECTION CRITERIA
Studies were included based on the STARD checklist, for which the ES and CMA diagnostic yields were calculated.
DATA COLLECTION AND ANALYSIS
Meta-analysis was performed on the included studies using a random-effects model and subgroup analysis to define the risk difference between them.
MAIN RESULTS
We included 11 studies representing 779 fetuses that implemented ES along with imaging techniques. The pooled ES diagnostic yield in fetuses with BAs detected through magnetic resonance imaging (MRI) and ultrasonography was 26.53%, compared with 3.46% for CMA. The risk difference between ES and CMA for complex BAs was 0.36 [95% confidence interval (CI) 0.24-0.47], which was higher than for single BAs (0.22; 95% CI 0.18-0.25].
CONCLUSIONS
ES is a useful method with a significantly higher diagnostic yield than CMA for genetic assessment of fetuses with complex BAs detected by imaging techniques. Moreover, ES could be applied to suspected fetuses with related family histories to predict congenital diseases with high efficiency.
PubMed: 37932235
DOI: 10.1111/1471-0528.17710 -
Scandinavian Journal of Immunology Jun 2016Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to... (Meta-Analysis)
Meta-Analysis Review
Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to identify the tumour-associated autoantibodies with the greatest diagnostic potential. Systematic searches were conducted using PubMed and Web of Science. The most studied tumour-associated autoantibody was included in a meta-analysis, and its clinical value was determined using Fagan's nomogram. The analysis included 84 studies regarding tumour-associated autoantibodies with the diagnostic value. Anti-p53 antibody was the most frequently studied autoantibody, followed by autoantibodies against MUC1, HER2 and cyclin B1. Although individual tumour-associated autoantibodies showed low diagnostic sensitivity, combinations of autoantibodies offered relatively high sensitivity. Enzyme-linked immunosorbent assay (ELISA) was the most common detection method, and nucleic acid programmable protein microarrays appeared preferable to common protein microarrays. As the most commonly studied autoantibody, anti-p53 antibody was included in a meta-analysis. When it had been detected using ELISA and cut-off values were defined as the mean +2 or 3 standard deviations, the summary area under the receiver operating characteristic curve for the presence of BC was 0.78. Fagan's nomogram showed post-test probabilities of 32% and 6% for positive and negative results, respectively. Mammography might be supplemented by the use of tumour-associated autoantibodies as biomarkers for BC diagnosis in younger women with increased risks of BC. Even though several studies have investigated the diagnostic use of tumour-associated autoantibodies as biomarkers for BC detection, a high-quality prospective study is needed to validate their diagnostic value in practice.
Topics: Animals; Biomarkers, Tumor; Breast Neoplasms; Cyclin B1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Mammography; Mucin-1; Predictive Value of Tests; Protein Array Analysis; Receptor, ErbB-2; Reference Standards; Sensitivity and Specificity; Tumor Suppressor Protein p53
PubMed: 26991924
DOI: 10.1111/sji.12430 -
DNA and Cell Biology Mar 2020Diabetes mellitus (DM) is one of the growing public health threats globally and as one of the common serious microvascular complications of DM, diabetic retinopathy (DR)... (Meta-Analysis)
Meta-Analysis
Diabetes mellitus (DM) is one of the growing public health threats globally and as one of the common serious microvascular complications of DM, diabetic retinopathy (DR) is the leading cause of irreversible visual impairments and blindness. There is growing concern about the role of microRNAs (miRNAs) in the pathogenesis of DR. This meta-analysis was designed to collect those published miRNA expression profiling studies that compared the miRNA expression profiles in the biological samples of DR patients with those in the control group. Eight publications were finally included in the meta-analysis, and a total of 93 differentially expressed miRNAs were reported. Although six miRNAs were reported in at least two studies and with the consistent direction, after stratification by the type of biological samples, miR-320a was consistently reported to be upregulated in two serum sample-based studies and miR-423-5p was consistently reported to be upregulated in two vitreous humor sample-based studies. miR-27b was consistently reported to be downregulated in two serum sample-based studies. In conclusion, the results of this meta-analysis of human DR miRNAs' expression profiling studies might provide some clues of the potential biomarkers of DR. Further investigation of the mechanisms of miRNAs and more external validation studies are warranted with the aim of developing new diagnostic markers for preventing or reversing DR.
Topics: Adult; Aged; Diabetic Retinopathy; Female; Gene Expression Profiling; Humans; Male; MicroRNAs; Microarray Analysis; Middle Aged; Up-Regulation; Vitreous Body
PubMed: 32101049
DOI: 10.1089/dna.2019.4942 -
Journal of Clinical Medicine Oct 2021To determine the diagnostic yield of exome sequencing (ES), a microarray analysis was carried out of fetuses with recurrent fetal structural anomalies (with similar... (Review)
Review
To determine the diagnostic yield of exome sequencing (ES), a microarray analysis was carried out of fetuses with recurrent fetal structural anomalies (with similar anomalies in consecutive pregnancies). This is a systematic review conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The selected studies describing ES in fetuses with recurrent fetal malformation were assessed using the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria for risk of bias. Incidence was used as the pooled effect size by single-proportion analysis using random-effects modeling (weighted by inverse of variance). We identified nine studies on ES diagnostic yield that included 140 fetuses with recurrent structural anomalies. A pathogenic or likely pathogenic variant was found in 57 fetuses, resulting in a 40% (95%CI: 26% to 54%) incremental performance pool of ES. As expected, the vast majority (86%: 36/42) of the newly identified diseases had a recessive inheritance pattern, and among these, 42% (15/36) of variants were found in homozygosity. Meckel syndrome was the monogenic disease most frequently found, although the genes involved were diverse. The ES diagnostic yield in pregnancies with recurrent fetal structural anomalies was 40% (57/140). Homozygous disease-causing variants were found in 36% (15/57) of the newly identified monogenic disorders.
PubMed: 34682862
DOI: 10.3390/jcm10204739 -
Ultrasound in Obstetrics & Gynecology :... Jun 2022To determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with multisystem structural... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with multisystem structural anomalies (at least two major anomalies in different anatomical systems).
METHOD
This was a systematic review conducted in accordance with PRISMA guidelines. Searching PubMed, Web of Knowledge and Cochrane database, we identified studies describing ES, whole-genome and/or next-generation sequencing in fetuses with multisystem malformations. Included were observational studies involving five or more eligible fetuses. A fetus was eligible for inclusion if it had at least two major anomalies of different anatomical systems and a negative CMA or karyotyping result. Only positive variants classified as likely pathogenic or pathogenic determined to be causative of the fetal phenotype were considered. A negative CMA or karyotype result was treated as the reference standard. The diagnostic yield of the primary outcome was calculated by single-proportion analysis using random-effects modeling. A subgroup analysis was performed to compare the diagnostic yield of the solo approach (fetus alone sequenced) with that of the trio approach (fetus and both parents sequenced).
RESULTS
Seventeen articles with data on ES diagnostic yield, including 694 individuals with multisystem malformations, were identified. Overall, a pathogenic or likely pathogenic variant potentially causative of the fetal phenotype was found in 213 fetuses, giving a 33% (95% CI, 27-40%) incremental yield of ES. A stratified analysis showed similar diagnostic yields of ES using the solo approach (30%; 95% CI, 11-52%) and the trio approach (35%; 95% CI, 26-44%).
CONCLUSIONS
ES applied in fetuses with multisystem structural anomalies was able to identify a potentially causative gene when CMA or karyotyping had failed to do so in an additional one-third of cases. No differences were observed between the solo and trio approaches for ES. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Exome; Female; Fetus; Humans; Karyotyping; Pregnancy; Prenatal Diagnosis; Exome Sequencing
PubMed: 35041238
DOI: 10.1002/uog.24862 -
PloS One 2016Pre-eclampsia (PE) is a serious multi-factorial disorder of human pregnancy. It is associated with changes in the expression of placental genes. Recent transcription... (Comparative Study)
Comparative Study Meta-Analysis Review
Pre-eclampsia (PE) is a serious multi-factorial disorder of human pregnancy. It is associated with changes in the expression of placental genes. Recent transcription profiling of placental genes with microarray analyses have offered better opportunities to define the molecular pathology of this disorder. However, the extent to which placental gene expression changes in PE is not fully understood. We conducted a systematic review of published PE and normal pregnancy (NP) control placental RNA microarrays to describe the similarities and differences between NP and PE placental gene expression, and examined how these differences could contribute to the molecular pathology of the disease. A total of 167 microarray samples were available for meta-analysis. We found the expression pattern of one group of genes was the same in PE and NP. The review also identified a set of genes (PE unique genes) including a subset, that were significantly (p < 0.05) down-regulated in pre-eclamptic placentae only. Using class prediction analysis, we further identified the expression of 88 genes that were highly associated with PE (p < 0.05), 10 of which (LEP, HTRA4, SPAG4, LHB, TREM1, FSTL3, CGB, INHA, PROCR, and LTF) were significant at p < 0.001. Our review also suggested that about 30% of genes currently being investigated as possibly of importance in PE placenta were not consistently and significantly affected in the PE placentae. We recommend further work to confirm the roles of the PE unique and associated genes, currently not being investigated in the molecular pathology of the disease.
Topics: Female; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Humans; Microarray Analysis; Placenta; Pre-Eclampsia; Pregnancy; RNA, Messenger; ROC Curve; Transcriptome; Trophoblasts
PubMed: 27560381
DOI: 10.1371/journal.pone.0161504 -
Cellular Physiology and Biochemistry :... 2015Aberrant microRNA expression has the potential to be used for early diagnosis of gastric cancer or to predict survival and treatment response. This study performed a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Aberrant microRNA expression has the potential to be used for early diagnosis of gastric cancer or to predict survival and treatment response. This study performed a systematic review and meta-analysis of altered miRNAs in gastric cancer in order to assess the use of miRNAs as novel biomarkers for early detection and prognosis prediction of gastric cancer.
METHODS
We retrieved published articles from the PubMed online database and obtained different sets of data on miRNAs expression profiling in gastric cancer and highlighted the most frequently dysregulated miRNAs in gastric cancer. We then extracted studies that used quantitative RT-PCR and then pooled them together by using meta-disc software (version 1.4).
RESULTS
We found that there were 47 aberrantly expressed miRNAs in gastric cancer (29 up-regulated and 18 down-regulated) that were most frequently reported in the literature. In publications that provided information on specific miRNA expression vs. diagnostic value, the pooled data showed good sensitivity and specificity as well as high levels of overall accuracy. However, specimen types could be a factor that introduces substantial heterogeneity. Published studies also showed association of altered miRNA expression with clinicopathological data from gastric cancer patients.
CONCLUSION
Thus, various miRNAs are differentially expressed in gastric cancer and some of them could be further evaluated as biomarkers for early diagnosis of gastric cancer and prediction of prognosis or treatment response.
Topics: Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Oligonucleotide Array Sequence Analysis; Prognosis; Stomach Neoplasms
PubMed: 25633747
DOI: 10.1159/000369750 -
Scientific Reports Sep 2017Temporal lobe epilepsy (TLE) is a common chronic neurological disease in humans. A number of studies have demonstrated differential expression of miRNAs in the... (Meta-Analysis)
Meta-Analysis
Temporal lobe epilepsy (TLE) is a common chronic neurological disease in humans. A number of studies have demonstrated differential expression of miRNAs in the hippocampus of humans with TLE and in animal models of experimental epilepsy. However, the dissimilarities in experimental design have led to largely discordant results across these studies. Thus, a comprehensive comparison is required in order to better characterize miRNA profiles obtained in various post-status epilepticus (SE) models. We therefore created a database and performed a meta-analysis of differentially expressed miRNAs across 3 post-SE models of epileptogenesis (electrical stimulation, pilocarpine and kainic acid) and human TLE with hippocampal sclerosis (TLE-HS). The database includes data from 11 animal post-SE studies and 3 human TLE-HS studies. A total of 378 differentially expressed miRNAs were collected (274 up-regulated and 198 down-regulated) and analyzed with respect to the post-SE model, time point and animal species. We applied the novel robust rank aggregation method to identify consistently differentially expressed miRNAs across the profiles. It highlighted common and unique miRNAs at different stages of epileptogenesis. The pathway analysis revealed involvement of these miRNAs in key pathogenic pathways underlying epileptogenesis, including inflammation, gliosis and deregulation of the extracellular matrix.
Topics: Animals; Biomarkers; Computational Biology; Disease Models, Animal; Epilepsy, Temporal Lobe; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Genetic Association Studies; Genetic Predisposition to Disease; Humans; MicroRNAs; Oligonucleotide Array Sequence Analysis; Signal Transduction; Species Specificity
PubMed: 28912503
DOI: 10.1038/s41598-017-11510-8