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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 -
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 -
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 -
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 -
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 -
Diagnostics (Basel, Switzerland) May 2022Cardiovascular malformations (CVM) represent the most common structural anomalies, occurring in 0.7% of live births. The CVM prenatal suspicion should prompt an accurate... (Review)
Review
Cardiovascular malformations (CVM) represent the most common structural anomalies, occurring in 0.7% of live births. The CVM prenatal suspicion should prompt an accurate investigation with fetal echocardiography and the assessment through genetic counseling and testing. In particular, chromosomal microarray analysis (CMA) allows the identification of copy number variations. We performed a systematic review and meta-analysis of the literature, studying the incremental diagnostic yield of CMA in fetal isolated CVM, scoring yields for each category of heart disease, with the aim of guiding genetic counseling and prenatal management. At the same time, we report 59 fetuses with isolated CVM with normal karyotype who underwent CMA. The incremental CMA diagnostic yield in fetuses with isolated CVM was 5.79% (CI 5.54-6.04), with conotruncal malformations showing the higher detection rate (15.93%). The yields for ventricular septal defects and aberrant right subclavian artery were the lowest (2.64% and 0.66%). Other CVM ranged from 4.42% to 6.67%. In the retrospective cohort, the diagnostic yield was consistent with literature data, with an overall CMA diagnostic yield of 3.38%. CMA in the prenatal setting was confirmed as a valuable tool for investigating the causes of fetal cardiovascular malformations.
PubMed: 35741137
DOI: 10.3390/diagnostics12061328 -
BMJ Global Health Oct 2023Microarray patches (MAPs) deliver vaccines to the epidermis and the upper dermis, where abundant immune cells reside. There are several potential benefits to using MAPs,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Microarray patches (MAPs) deliver vaccines to the epidermis and the upper dermis, where abundant immune cells reside. There are several potential benefits to using MAPs, including reduced sharps risk, thermostability, no need for reconstitution, tolerability and self-administration. We aimed to explore and evaluate the immunogenicity, safety, usability and acceptability of MAPs for vaccination.
METHODS
We searched CINAHL, Cochrane Library, Ovid Embase, Ovid MEDLINE and Web of Science from inception to January 2023. Eligibility criteria included all research studies in any language, which examined microarrays or microneedles intended or used for vaccination and explored immunogenicity, safety, usability or acceptability in their findings. Two reviewers conducted title and abstract screening, full-text reviewing and data extraction.
RESULTS
Twenty-two studies were included (quantitative=15, qualitative=2 and mixed methods=5). The risk of bias was mostly low, with two studies at high risk of bias. Four clinical trials were included, three using influenza antigens and one with Japanese encephalitis delivered by MAP. A meta-analysis indicated similar or higher immunogenicity in influenza MAPs compared with needle and syringe (N&S) (standardised mean difference=10.80, 95% CI: 3.51 to 18.08, p<0.00001). There were no significant differences in immune cell function between MAPs and N&S. No serious adverse events were reported in MAPs. Erythema was more common after MAP application than N&S but was brief and well tolerated. Lower pain scores were usually reported after MAP application than N&S. Most studies found MAPs easy to use and highly acceptable among healthcare professionals, laypeople and parents.
CONCLUSION
MAPs for vaccination were safe and well tolerated and evoked similar or enhanced immunogenicity than N&S, but further research is needed. Vaccine uptake may be increased using MAPs due to less pain, enhanced thermostability, layperson and self-administration. MAPs could benefit at-risk groups and low and middle-income countries.
PROSPERO REGISTRATION NUMBER
CRD42022323026.
Topics: Humans; Influenza, Human; Vaccination; Vaccines; Pain
PubMed: 37827725
DOI: 10.1136/bmjgh-2023-012247 -
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 -
Diagnostics (Basel, Switzerland) Feb 2022Fetal malformations occur in 2-3% of pregnancies. They require invasive procedures for cytogenetics and molecular testing. "Structural anomalies" include non-transient... (Review)
Review
Fetal malformations occur in 2-3% of pregnancies. They require invasive procedures for cytogenetics and molecular testing. "Structural anomalies" include non-transient anatomic alterations. "Soft markers" are often transient minor ultrasound findings. Anomalies not fitting these definitions are categorized as "dynamic". This meta-analysis aims to evaluate the diagnostic yield and the rates of variants of uncertain significance (VUSs) in fetuses undergoing molecular testing (chromosomal microarray (CMA), exome sequencing (ES), genome sequencing (WGS)) due to ultrasound findings. The CMA diagnostic yield was 2.15% in single soft markers (vs. 0.79% baseline risk), 3.44% in multiple soft markers, 3.66% in single structural anomalies and 8.57% in multiple structural anomalies. Rates for specific subcategories vary significantly. ES showed a diagnostic rate of 19.47%, reaching 27.47% in multiple structural anomalies. WGS data did not allow meta-analysis. In fetal structural anomalies, CMA is a first-tier test, but should be integrated with karyotype and parental segregations. In this class of fetuses, ES presents a very high incremental yield, with a significant VUSs burden, so we encourage its use in selected cases. Soft markers present heterogeneous CMA results from each other, some of them with risks comparable to structural anomalies, and would benefit from molecular analysis. The diagnostic rate of multiple soft markers poses a solid indication to CMA.
PubMed: 35328129
DOI: 10.3390/diagnostics12030575 -
Experimental Biology and Medicine... Jan 2020Association between microRNA (miRNA) expression signatures and atrial fibrillation has been evaluated with inconsistent findings in different studies. This study aims to... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Association between microRNA (miRNA) expression signatures and atrial fibrillation has been evaluated with inconsistent findings in different studies. This study aims to identify miRNAs that actually play vital role in pathophysiological process of atrial fibrillation and explore miRNA-targeted genes and the involved pathways. Relevant studies were retrieved from the electronic databases of Embase, Medline, and Cochrane Library to determine the miRNA expression profiles between atrial fibrillation subjects and non-atrial fibrillation controls. Robustness of results was assessed using sensitivity analysis. Subgroup analyses were performed based on species, miRNA detection method, sample source, and ethnicity. Quality assessment of studies was independently conducted according to QUADAS-2. Bioinformatics analysis was applied to explore the potential genes and pathways associated with atrial fibrillation, which were targeted by differentially expressed miRNAs. Form of pooled results was shown as log10 odds ratios (logORs) with 95% confidence intervals (CI), and random-effects model was used. In total, 40 articles involving 283 differentially expressed miRNAs were reported. And 51 significantly dysregulated miRNAs were identified in consistent direction, with 22 upregulated and 29 downregulated. Among above-mentioned miRNAs, miR-223-3p (logOR 6.473; P < 0.001) was the most upregulated, while miR-1-5p (logOR 7.290; P < 0.001) was the most downregulated. Subgroup analysis confirmed 53 significantly dysregulated miRNAs (21 upregulated and 32 downregulated) in cardiac tissue, with miRNA-1-5p and miRNA-223-3p being the most upregulated and downregulated miRNAs, respectively. Additionally, miR-328 and miR-1-5p were highly blood-specific, and miR-133 was animal-specific. In the detection method sub-groups, miRNA-29b and miRNA-223-3p were differentially expressed consistently. Four miRNAs, including miRNA-223-3p, miRNA-21, miRNA-328, and miRNA-1-5p, were consistently dysregulated in both Asian and non-Asian. Results of sensitivity analysis showed that 47 out of 51 (92.16%) miRNAs were dysregulated consistently. Totally, 51 consistently dysregulated miRNAs associated with atrial fibrillation were confirmed in this study. Five important miRNAs, including miR-29b, miR-328, miR-1-5p, miR-21, and miR-223-3p may act as potential biomarkers for atrial fibrillation.
IMPACT STATEMENT
Atrial fibrillation (AF) is considered as the most common arrhythmia, and it subsequently causes serious complications including thrombosis and heart failure that increase the social burden. The definite mechanisms underlying AF pathogenesis remain complicated and unclear. Many studies attempted to discover the transcriptomic changes using microarray technologies, and the present studies for this hot topic have assessed individual miRNAs profiles for AF. However, results of different articles are controversial and not each reported miRNA is actually associated with the pathogenesis of AF. The present systematic review and meta-analysis identified that 51 consistently dysregulated miRNAs were associated with AF. Of these miRNAs, five miRNAs (miRNA-1-5p, miRNA-328, miRNA-29b, miRNA-21, and miRNA-223-3p) may act as novel biomarkers for AF. The findings could offer a better description of the biological characteristics of miRNAs, meanwhile might serve as new target for the intervention and monitoring AF in future studies.
Topics: Animals; Atrial Fibrillation; Computational Biology; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Humans; MicroRNAs; Up-Regulation
PubMed: 31766887
DOI: 10.1177/1535370219890303