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BJOG : An International Journal of... Jan 2014Approximately 50% of spontaneous miscarriages are associated with chromosome abnormalities. Identification of these karyotypic abnormalities helps to estimate recurrence... (Comparative Study)
Comparative Study Meta-Analysis Review
Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis.
BACKGROUND
Approximately 50% of spontaneous miscarriages are associated with chromosome abnormalities. Identification of these karyotypic abnormalities helps to estimate recurrence risks in future pregnancies. Chromosomal microarray analysis (CMA) is transforming clinical cytogenetic practice with its ability to examine the human genome at increasingly high resolution.
OBJECTIVES
The aim of this study was to determine whether CMA testing on the products of conception following miscarriage provides better diagnostic information compared with conventional karyotyping.
SEARCH STRATEGY
MEDLINE (from 1996 to December 2012), EMBASE (from 1974 to December 2012), and CINAHL (from 1996 to December 2012) databases were searched electronically.
SELECTION CRITERIA
Studies were selected if CMA was used on products of conception following miscarriage, alongside conventional karyotyping.
DATA COLLECTION AND ANALYSIS
Nine papers were included in the systematic review and meta-analysis. All statistical analyses were performed using stata 11.0 (Stata Corp., College Station, TX, USA).
MAIN RESULTS
There was agreement between CMA and karyotyping in 86.0% of cases (95% CI 77.0-96.0%). CMA detected 13% (95% CI 8.0-21.0) additional chromosome abnormalities over conventional full karyotyping. In addition, traditional, full karyotyping detected 3% (95% CI 1.0-10.0%) additional abnormalities over CMA. The incidence of a variant of unknown significance (VOUS) being detected was 2% (95% CI 1.0-10.0%).
AUTHOR'S CONCLUSIONS
Compared with karyotyping, there appears to be an increased detection rate of chromosomal abnormalities when CMA is used to analyse the products of conception; however, some of these abnormalities are VOUS, and this information should be provided when counselling women following miscarriage and when taking consent for the analysis of miscarriage products by CMA.
Topics: Abortion, Spontaneous; Chromosome Aberrations; Chromosome Disorders; Comparative Genomic Hybridization; Female; Humans; Karyotyping; Microarray Analysis; Pregnancy
PubMed: 23859082
DOI: 10.1111/1471-0528.12382 -
Molecular Cancer Therapeutics Aug 2011Despite intensive research efforts, within-stage survival rates for melanoma vary widely. Pursuit of molecular biomarkers with improved prognostic significance over... (Review)
Review
Despite intensive research efforts, within-stage survival rates for melanoma vary widely. Pursuit of molecular biomarkers with improved prognostic significance over clinicohistological measures has produced extensive literature. Reviews have synthesized these data, but none have systematically partitioned high-quality studies from the remainder across different molecular methods nor examined system properties of that output. Databases were searched for studies analyzing protein expression by immunohistochemistry (n = 617, extending the only systematic review to date by 102 studies) or for gene expression microarray studies (n = 45) in melanoma in relation to outcome. REMARK-derived criteria were applied to identify high-quality studies. Biomarkers and pathways were functionally assessed by using gene ontology software. Most manuscripts did not meet REMARK-based criteria, an ongoing trend that can impede translational research. Across REMARK-compliant literature, 41 proteins were significantly associated with outcome. Multimarker tests consistently emerged among the most promising potential biomarkers, indicating a need to continue assessing candidates in that composite setting. Twenty-one canonical pathways were populated by outcome-related proteins but not by those that failed to show such an association; we propose that this set of pathways warrants closer investigation to understand drivers of poor outcome in melanoma. Two-gene expression microarray studies met REMARK-based criteria reflecting a genuine paucity of literature in the area. The 254 outcome-related genes were examined for correspondences with the systematically identified protein signature. This analysis highlighted proliferating cell nuclear antigen and survivin as priorities for further examination as biomarkers in melanoma prognosis, and illustrated ongoing need to integrate alternative approaches to biomarker discovery in melanoma translational research.
Topics: Biomarkers, Tumor; Computational Biology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Melanoma; Prognosis
PubMed: 21659462
DOI: 10.1158/1535-7163.MCT-10-0901 -
Ultrasound in Obstetrics & Gynecology :... May 2019To assess the added value of chromosomal microarray analysis (CMA) over conventional karyotyping to assess the genetic causes in stillbirth. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the added value of chromosomal microarray analysis (CMA) over conventional karyotyping to assess the genetic causes in stillbirth.
METHODS
To identify relevant studies, published in English or Spanish and without publication time restrictions, we performed a systematic search of PubMed, SCOPUS and ISI Web of Science databases, The Cochrane Library and the PROSPERO register of systematic reviews, for case series of fetal loss ≥ 20 weeks of gestation, with normal or suspected normal karyotype, undergoing CMA and with at least five subjects analyzed. To investigate quality, two reviewers evaluated independently the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. For the meta-analysis, the incremental yield of CMA over karyotyping was assessed by single-proportion analysis using a random-effects model (weighting by inverse variance). We assessed heterogeneity between studies and performed a sensitivity analysis and a subgroup analysis of structurally abnormal (malformed or growth-restricted) and normal fetuses.
RESULTS
Included in the meta-analysis were seven studies involving 903 stillborn fetuses which had normal karyotype. The test success rate achieved by conventional cytogenetic analysis was 75%, while that for CMA was 90%. The incremental yield of CMA over conventional karyotyping based on the random-effects model was 4% (95% CI, 3-5%) for pathogenic copy-number variants (pCNVs) and 8% (95% CI, 4-17%) for variants of unknown significance. Subgroup analysis showed a 6% (95% CI, 4-10%) incremental yield of CMA for pCNVs in structurally abnormal fetuses and 3% (95% CI, 1-5%) incremental yield for those in structurally normal fetuses. The pCNV found most commonly was del22q11.21.
CONCLUSIONS
CMA, incorporated into the stillbirth work-up, improves both the test success rate and the detection of genetic anomalies compared with conventional karyotyping. To achieve a genetic diagnosis in stillbirth is particularly relevant for the purpose of counseling regarding future pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Chromosome Aberrations; Female; Fetal Diseases; Humans; Karyotyping; Microarray Analysis; Pregnancy; Stillbirth
PubMed: 30549343
DOI: 10.1002/uog.20198 -
International Journal of Molecular... Jun 2020The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the... (Meta-Analysis)
Meta-Analysis Review
AIM
The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.
MATERIALS AND METHODS
Human and animal studies were included when evaluating expression of miRNAs between health and different forms/stages of diseases, in which microarray and/or real-time polymerase chain reaction (RT-PCR) was carried out to detect fold changes in gene expression. After full-text analysis, 43 articles were considered for a qualitative assessment, and 16 miRNAs were selected to perform meta-analysis.
RESULTS
Based on human studies, results showed an overall upregulation of most of the evaluated miRNAs in periodontitis, with miRNA-142-3p and miRNA-146a being the most conclusive on both microarray and RT-PCR values and potentially serving as diagnostic biomarkers for disease activity. Conversely, miR-155 was the only miRNA revealing a statistically significant difference (SSD) ( < 0.05*) in experimental periodontitis models from RT-PCR values. Scarce scientific evidence is available from peri-implant diseases, however, most explored miRNAs in peri-implantitis were downregulated except for miR-145.
CONCLUSIONS
Although our results revealed that a distinct differential expression of specific miRNAs can be noted between the state of health and disease, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases. MeSH Terms: periodontitis, peri-implantitis, epigenomics, microarray analysis, real-time polymerase chain reaction, microRNAs.
CLINICAL RELEVANCE
Scientific background: Although most research identified different expression levels of miRNAs in periodontal and peri-implant diseases compared to their counterparts, their actual role in the pathogenesis of these conditions remains unclear. Therefore, we aimed to present a systematic review and meta-analysis on the expression patterns of miRNAs in periodontitis and peri-implantitis, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.
PRINCIPAL FINDINGS
In periodontitis-related studies, miRNA-142-3p and miRNA-146a were the most conclusive on both microarray and RT-PCR values. Scarce scientific evidence is available from peri-implant diseases.
PRACTICAL IMPLICATIONS
Both miRNA-142-3p and miRNA-146a might serve as future diagnostic biomarkers for disease activity in periodontitis. Yet, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases.
Topics: Animals; Biomarkers; Humans; MicroRNAs; Oligonucleotide Array Sequence Analysis; Peri-Implantitis; Periodontitis
PubMed: 32532036
DOI: 10.3390/ijms21114147 -
Urologic Oncology May 2022Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated. This study aims to define gene expression profiles in MIBC and to identify potential candidate genes and pathways.
OBJECTIVES
To review and evaluate gene expression studies in MIBC through publicly available RNA sequencing (RNA-Seq) and microarray data in order to identify potential prognostic and therapeutic targets for MIBC.
METHODS
A systematic literature search of the Ovid MEDLINE, PubMed, and Wiley Cochrane Central Register of Controlled Trials databases was performed using the terms "gene," "gene expression," and "bladder cancer" January 1, 1990 through March 2021 focused on populations with MIBC.
RESULTS
In the final analysis, GEO datasets were included. Fixed effect model was employed in the meta-analysis. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in MIBC were performed using ImaGEO and GeneMANIA software. A heatmap for the upregulated and downregulated genes was generated along with the correlated pathways.
CONCLUSION
A total of 9 genes were reported in this analysis. Six genes were reported as upregulated (ProTα, SPINT1, UBE2E1, RAB25, KPNB1, HDAC1) and 3 genes as downregulated (NUP188, IPO13, NUP124). Genes were found to be involved in "ubiquitin mediated proteolysis," "protein processing in endoplasmic reticulum," "transcriptional misregulation in cancer," and "RNA transport" pathways.
Topics: Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Male; Muscles; Neoplasm Invasiveness; Prognosis; Urinary Bladder Neoplasms; rab GTP-Binding Proteins
PubMed: 35039218
DOI: 10.1016/j.urolonc.2021.11.003 -
Cancers Jan 2023Cervical cancer is the leading cause of cancer-related death among women in developing countries. However, no comprehensive molecular mechanism for cervical cancer has... (Review)
Review
Cervical cancer is the leading cause of cancer-related death among women in developing countries. However, no comprehensive molecular mechanism for cervical cancer has been established, as many studies were small-cohort studies conducted with small sample sizes. A thorough literature search was performed using the PubMed, Scopus, EBSCOhost, and Science Direct databases. Medical Subject Heading (MeSH) terms such as "Uterine Cervical Neoplasms" and "gene expression" were used as the keywords in all fields. A total of 4027 studies were retrieved, and only clinical studies, which used the microarray method to identify differentially expressed genes (DEGs) in the cervical tissue of cervical cancer patients, were selected. Following the screening, 6 studies were selected and 1128 DEGs were extracted from the data. Sixty-two differentially expressed genes from at least two studies were selected for further analysis by DAVID, STRING, and Cytoscape software. In cervical cancer pathogenesis, three significant clusters with high intermolecular interactions from the Protein-Protein Interaction (PPI) network complex revealed three major molecular mechanisms, including cell signaling, cell cycle, and cell differentiation. Subsequently, eight genes were chosen as the candidate genes based on their involvement in the relevant gene ontology (GO) and their interaction with other genes in the PPI network through undirected first neighbor nodes. The present systematic review improves our understanding of the molecular mechanism of cervical cancer and the proposed genes that can be used to expand the biomarker panel in the screening for cervical cancer. The targeted genes may be beneficial for the development of better treatment strategies.
PubMed: 36765810
DOI: 10.3390/cancers15030853 -
Ultrasound in Obstetrics & Gynecology :... Jan 2015Array comparative genomic hybridization (aCGH) is a molecular cytogenetic technique that is able to detect the presence of copy number variants (CNVs) within the genome.... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
Array comparative genomic hybridization (aCGH) is a molecular cytogenetic technique that is able to detect the presence of copy number variants (CNVs) within the genome. The detection rate of imbalances by aCGH compared to standard karyotyping and 22q11 microdeletion analysis by fluorescence in-situ hybridization (FISH), in the setting of prenatally-diagnosed cardiac malformations, has been reported in several studies. The objective of our study was to perform a systematic literature review and meta-analysis to document the additional diagnostic gain of using aCGH in cases of congenital heart disease (CHD) diagnosed by prenatal ultrasound examination, with the aim of assisting clinicians to determine whether aCGH analysis is warranted when an ultrasonographic diagnosis of CHD is made, and to guide counseling in this setting.
METHODS
Articles in PubMed, EMBASE and Web of Science databases from January 2007 to September 2014 describing CNVs in prenatal cases of CHD were included. Search terms were: 'array comparative genomic hybridization', 'copy number variants' and 'fetal congenital heart defects'. Articles regarding karyotyping or 22q11 deletion only were excluded.
RESULTS
Thirteen publications (including 1131 cases of CHD) met the inclusion criteria for the analysis. Meta-analysis indicated an incremental yield of 7.0% (95% CI, 5.3-8.6%) for the detection of CNVs using aCGH, excluding aneuploidy and 22q11 microdeletion cases. Subgroup results showed a 3.4% (95% CI, 0.3-6.6%) incremental yield in isolated CHD cases, and 9.3% (95% CI, 6.6-12%) when extracardiac malformations were present. Overall, an incremental yield of 12% (95% CI, 7.6-16%) was found when 22q11 deletion cases were included. There was an additional yield of 3.4% (95% CI, 2.1-4.6%) for detecting variants of unknown significance (VOUS).
CONCLUSIONS
In this review we provide an overview of published data and discuss the benefits and limitations of using aCGH. If karyotyping and 22q11 microdeletion analysis by FISH are normal, using aCGH has additional value, detecting pathogenic CNVs in 7.0% of prenatally diagnosed CHD, with a 3.4% additional yield of detecting VOUS.
Topics: Comparative Genomic Hybridization; DNA Copy Number Variations; Female; Genetic Counseling; Heart Defects, Congenital; Humans; Karyotyping; Microarray Analysis; Pregnancy; Prenatal Diagnosis
PubMed: 25319878
DOI: 10.1002/uog.14695 -
Oncotarget Sep 2016Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is poorly responsive to current treatments. Minimally invasive, specific, and sensitive biomarkers providing early and effective diagnosis in high-risk patients are urgently needed. MicroRNAs (miRNAs, miRs) are endogenous, non-coding, small RNAs with established diagnostic value in cancer and pollution exposure. A systematic review and a qualitative meta-analysis were conducted to identify high-confidence miRNAs that can serve as biomarkers of asbestos exposure and MM.
METHODS
The major biomedical databases were systematically searched for miRNA expression signatures related to asbestos exposure and MM. The qualitative meta-analysis applied a novel vote-counting method that takes into account multiple parameters. The most significant miRNAs thus identified were then subjected to functional and bioinformatic analysis to assess their biomarker potential.
RESULTS
A pool of deregulated circulating and tissue miRNAs with biomarker potential for MM was identified and designated as "mesomiRs" (MM-associated miRNAs). Comparison of data from asbestos-exposed and MM subjects found that the most promising candidates for a multimarker signature were circulating miR-126-3p, miR-103a-3p, and miR-625-3p in combination with mesothelin. The most consistently described tissue miRNAs, miR-16-5p, miR-126-3p, miR-143-3p, miR-145-5p, miR-192-5p, miR-193a-3p, miR-200b-3p, miR-203a-3p, and miR-652-3p, were also found to provide a diagnostic signature and should be further investigated as possible therapeutic targets.
CONCLUSION
The qualitative meta-analysis and functional investigation confirmed the early diagnostic value of two miRNA signatures for MM. Large-scale, standardized validation studies are needed to assess their clinical relevance, so as to move from the workbench to the clinic.
Topics: Asbestos; Biomarkers, Tumor; Computational Biology; Epigenesis, Genetic; GPI-Linked Proteins; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Mesothelin; Mesothelioma; Mesothelioma, Malignant; MicroRNAs; Oligonucleotide Array Sequence Analysis; Phenotype; Tissue Array Analysis; Tissue Distribution
PubMed: 27259231
DOI: 10.18632/oncotarget.9686 -
Acta Obstetricia Et Gynecologica... Nov 2019The aim of this systematic review was to explore the outcome of fetuses with a prenatal diagnosis of isolated talipes. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The aim of this systematic review was to explore the outcome of fetuses with a prenatal diagnosis of isolated talipes.
MATERIAL AND METHODS
Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched. The outcomes explored were: associated anomalies detected at follow-up ultrasound examination; fetal magnetic resonance imaging (MRI) and birth; chromosomal abnormalities detected with standard and chromosomal microarray analysis, intrauterine, neonatal, and perinatal death, and termination of pregnancy; rate of surgical and nonsurgical treatment; neurodevelopmental outcome; and false-positive rate of prenatal diagnosis. Meta-analyses of proportions were used to combine data.
RESULTS
Twenty-five studies (1567 fetuses) were included. Associated anomalies were detected in 7.8% (95% CI 0.1%-29.3%) of cases at follow-up ultrasound, and in 4.0% (95% CI 0.1%-13.2%) of cases, fetal MRI identified anomalies not detected at ultrasound assessment. Similarly, 7.0% (95% CI 3.4%-11.7%) of cases labeled as isolated talipes on prenatal imaging were found to have associated anomalies at birth. Abnormal karyotype was present in 3.6% (95% CI 1.7%-6.2%) of fetuses, whereas no anomaly was found at chromosomal microarray analysis, although this outcome was reported by only 1 study. Intrauterine death occurred in 0.99% (95% CI 0.4%-1.9%) of fetuses, whereas the corresponding figures for neonatal death and termination of pregnancy were 1.5% (95% CI 0.6%-2.6%) and 2.2% (95% CI 1.2%-3.4%), respectively. Surgical management of anomalies after birth was found in 41.7% (95% CI 27.0%-57.2%) of fetuses with isolated talipes, and 54.8% (95% CI 31.5%-77.0%) had nonsurgical management of the anomalies after birth. Abnormal neurodevelopmental outcome was reported in 7.6% (95% CI 1.0%-19.4%) of children, although this analysis was affected by the small number of included cases and short time of follow up.
CONCLUSIONS
Isolated talipes detected on prenatal ultrasound carries a generally good prognosis. The incidence of additional abnormalities detected on fetal MRI, aneuploidy, or neurodevelopmental disability is relatively low. However, longitudinal ultrasound assessment during pregnancy and a thorough postnatal evaluation are recommended to rule out associated anomalies that may significantly impact short- and long-term prognosis.
Topics: Conservative Treatment; Female; Follow-Up Studies; Humans; Incidence; Magnetic Resonance Imaging; Orthopedic Procedures; Pregnancy; Pregnancy Outcome; Prenatal Care; Prenatal Diagnosis; Risk Assessment; Talipes; Ultrasonography, Prenatal
PubMed: 31034582
DOI: 10.1111/aogs.13637 -
Genes May 2023Skeletal dysplasias are a group of diseases characterized by bone and joint abnormalities, which can be detected during prenatal ultrasound. Next-generation sequencing... (Review)
Review
Diagnostic Yield of Exome Sequencing in Fetuses with Sonographic Features of Skeletal Dysplasias but Normal Karyotype or Chromosomal Microarray Analysis: A Systematic Review.
Skeletal dysplasias are a group of diseases characterized by bone and joint abnormalities, which can be detected during prenatal ultrasound. Next-generation sequencing has rapidly revolutionized molecular diagnostic approaches in fetuses with structural anomalies. This review studies the additional diagnostic yield of prenatal exome sequencing in fetuses with prenatal sonographic features of skeletal dysplasias. This was a systematic review by searching PubMed for studies published between 2013 and July 2022 that identified the diagnostic yield of exome sequencing after normal karyotype or chromosomal microarray analysis (CMA) for cases with suspected fetal skeletal dysplasias based on prenatal ultrasound. We identified 10 out of 85 studies representing 226 fetuses. The pooled additional diagnostic yield was 69.0%. The majority of the molecular diagnoses involved de novo variants (72%), while 8.7% of cases were due to inherited variants. The incremental diagnostic yield of exome sequencing over CMA was 67.4% for isolated short long bones and 77.2% for non-isolated cases. Among phenotypic subgroup analyses, features with the highest additional diagnostic yield were an abnormal skull (83.3%) and a small chest (82.5%). Prenatal exome sequencing should be considered for cases with suspected fetal skeletal dysplasias with or without a negative karyotype or CMA results. Certain sonographic features, including an abnormal skull and small chest, may indicate a potentially higher diagnostic yield.
Topics: Pregnancy; Female; Humans; Prenatal Diagnosis; Exome Sequencing; Microarray Analysis; Fetus; Osteochondrodysplasias; Karyotype
PubMed: 37372383
DOI: 10.3390/genes14061203