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Epigenomics Sep 2022The aim of this systematic review and meta-analysis was to assess the evidence for the diagnostic effectiveness of human papillomavirus (HPV) methylation biomarkers for... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review and meta-analysis was to assess the evidence for the diagnostic effectiveness of human papillomavirus (HPV) methylation biomarkers for detection of cervical cancer. PubMed, Embase and Web of Science were searched. Nine articles focusing on HPV methylation for detection of precancerous and cancerous cervical lesions were included. The QUADAS-2 tool was used for quality assessment. The receiver operating characteristic (ROC) was the main diagnostic performance parameter extracted. Of the nine articles included in this study, seven were of moderate quality and two were of high quality. A meta-analysis of the ROC for 27 HPV methylation biomarkers revealed an overall pooled ROC of 0.770 (95% CI: 0.720-0.819; I: 98.4%; Q: 1537.4; p < 0.01). Four methylation biomarkers had strong diagnostic ability (ROC > 0.900), 17 were moderate (ROC: 0.7000-0.8999) and six were poor (ROC < 0.700). HPV methylation biomarkers hold significant promise as independent screening tests for the detection of cervical precancerous and cancerous lesions.
Topics: Alphapapillomavirus; Biomarkers; Early Detection of Cancer; Female; Humans; Methylation; Papillomaviridae; Papillomavirus Infections; Precancerous Conditions; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 36169190
DOI: 10.2217/epi-2022-0160 -
International Journal of Molecular... Aug 2022Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers... (Meta-Analysis)
Meta-Analysis Review
Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers to predict the response and outcome of current or newly designed therapies. While several molecular markers have been proposed as potential biomarkers for GBM, their uptake into clinical settings is slow and impeded by marker heterogeneity. Detailed assessment of prognostic and predictive value for biomarkers in well-defined clinical trial settings, if available, is scattered throughout the literature. Here we conducted a systematic review and meta-analysis to evaluate the prognostic and predictive significance of clinically relevant molecular biomarkers in GBM patients. Material and methods: A comprehensive literature search was conducted to retrieve publications from 3 databases (Pubmed, Cochrane and Embase) from January 2010 to December 2021, using specific terms. The combined hazard ratios (HR) and confidence intervals (95% CI) were used to evaluate the association of biomarkers with overall survival (OS) in GBM patients. Results: Twenty-six out of 1831 screened articles were included in this review. Nineteen articles were included in the meta-analyses, and 7 articles were quantitatively summarised. Fourteen studies with 1231 GBM patients showed a significant association of MGMT methylation with better OS with the pooled HR of 1.66 (95% CI 1.32−2.09, p < 0.0001, random effect). Five studies including 541 GBM patients analysed for the prognostic significance of IDH1 mutation showed significantly better OS in patients with IDH1 mutation with a pooled HR of 2.37 (95% CI 1.81−3.12; p < 0.00001]. Meta-analysis performed on 5 studies including 575 GBM patients presenting with either amplification or high expression of EGFR gene did not reveal any prognostic significance with a pooled HR of 1.31 (95% CI 0.96−1.79; p = 0.08). Conclusions: MGMT promoter methylation and IDH1 mutation are significantly associated with better OS in GBM patients. No significant associations were found between EGFR amplification or overexpression with OS.
Topics: Biomarkers; Biomarkers, Tumor; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Humans; Tumor Suppressor Proteins
PubMed: 36012105
DOI: 10.3390/ijms23168835 -
Journal of Crohn's & Colitis Mar 2023Over the past decade, the DNA methylome has been increasingly studied in peripheral blood of inflammatory bowel disease [IBD] patients. However, a comprehensive summary... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Over the past decade, the DNA methylome has been increasingly studied in peripheral blood of inflammatory bowel disease [IBD] patients. However, a comprehensive summary and meta-analysis of peripheral blood leukocyte [PBL] DNA methylation studies has thus far not been conducted. Here, we systematically reviewed all available literature up to February 2022 and summarized the observations by means of meta-analysis.
METHODS
We conducted a systematic search and critical appraisal of IBD-associated DNA methylation studies in PBL using the biomarker-based cross-sectional studies [BIOCROSS] tool. Subsequently, we performed meta-analyses on the summary statistics obtained from epigenome-wide association studies [EWAS] that included patients with Crohn's disease [CD], ulcerative colitis [UC] and/or healthy controls [HC].
RESULTS
Altogether, we included 15 studies for systematic review. Critical appraisal revealed large methodological and outcome heterogeneity between studies. Summary statistics were obtained from four studies based on a cumulative 552 samples [177 CD, 132 UC and 243 HC]. Consistent differential methylation was identified for 256 differentially methylated probes [DMPs; Bonferroni-adjusted p ≤ 0.05] when comparing CD with HC and 103 when comparing UC with HC. Comparing IBD [CD + UC] with HC resulted in 224 DMPs. Importantly, several of the previously identified DMPs, such as VMP1/TMEM49/MIR21 and RPS6KA2, were consistently differentially methylated across all studies.
CONCLUSION
Methodological homogenization of IBD epigenetic studies is needed to allow for easier aggregation and independent validation. Nonetheless, we were able to confirm previous observations. Our results can serve as the basis for future IBD epigenetic biomarker research in PBL.
Topics: Humans; DNA Methylation; Cross-Sectional Studies; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Membrane Proteins
PubMed: 35998097
DOI: 10.1093/ecco-jcc/jjac119 -
Current Pharmaceutical Design 2022We aimed to systematically evaluate the regulatory effect of arsenic on DNMTs and its downstream molecules in tumor cells and to provide a theoretical framework... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to systematically evaluate the regulatory effect of arsenic on DNMTs and its downstream molecules in tumor cells and to provide a theoretical framework revealing the specific mechanism of arsenic in the treatment of tumors.
METHODS
Meta-analysis was performed using RevMan 5.3 and Stata 12.0, and differences between groups were described as standardized mean difference.
RESULTS
We found out that compared with the control group, the expression of DNMT1, DNMT3a, DNMT3b, MMP-9 & β-catenin decreased and the expression of RECK and E-cadherin increased in the arsenic-treated group. Subgroup analysis showed that high-dose arsenic exposure (> 2 μmol/L) reduced the expression of DNMT1, DNMT3b, MMP-9, and β-catenin and promoted the expression of E-cadherin. Arsenic could decrease the level of DNMT1, MMP-9 & β-catenin and increase the level of E-cadherin with short-time arsenic intervention (≤ 48 h). Arsenic could reduce DNMT1, DNMT3a, DNMT3b & β-catenin in hematological tumor cells; under the effect of arsenic, the expression of DNMT1, DNMT3b, MMP-9 & β-catenin decreased in solid tumor cells. In addition, the regulation of arsenic on DNMT3a was dose-dependent in the range of arsenic concentration from 0 to 5.0 μmol/L. The dose, time, and cell types of arsenic intervention were the variables of heterogeneity.
CONCLUSION
Arsenic could inhibit the proliferation and viability of tumor cells, and its mechanism may be related to the reduction of DNMTs and regulation of the expression of its downstream molecules. Overall, arsenic may be a promising candidate for the treatment of tumors.
Topics: Humans; beta Catenin; Arsenic; Matrix Metalloproteinase 9; DNA Methylation; DNA (Cytosine-5-)-Methyltransferases; DNA (Cytosine-5-)-Methyltransferase 1; Cadherins; Cell Proliferation; GPI-Linked Proteins
PubMed: 35984018
DOI: 10.2174/1381612828666220818150959 -
CNS Neuroscience & Therapeutics Oct 2022Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno-oncology, this study aimed to assess the impact of multiple factors on GBM... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno-oncology, this study aimed to assess the impact of multiple factors on GBM immunotherapy prognosis and investigate the potential predictors.
METHODS
A quantitative meta-analysis was conducted using the random-effects model. Several potential factors were also reviewed qualitatively.
RESULTS
A total of 39 clinical trials were included after screening 1317 papers. Patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation [hazard ratio (HR) for overall survival (OS) = 2.30, p < 0.0001; HR for progression-free survival (PFS) = 2.10, p < 0.0001], gross total resection (HR for OS = 0.70, p = 0.02; HR for PFS = 0.56, p = 0.004), and no baseline steroid use (HR for OS = 0.52, p = 0.0002; HR for PFS = 0.61, p = 0.02) had a relatively significant favorable OS and PFS following immunotherapy. Patients with a Karnofsky Performance Status score < 80 (HR = 1.73, p = 0.0007) and undergoing two prior relapses (HR = 2.08, p = 0.003) were associated with worse OS. Age, gender, tumor programmed death-ligand 1 expression, and history of chemotherapy were not associated with survival outcomes. Notably, immunotherapy significantly improved the OS among patients undergoing two prior recurrences (HR = 0.40, p = 0.008) but not among patients in any other subgroups, as opposed to non-immunotherapy.
CONCLUSION
Several factors were associated with prognostic outcomes of GBM patients receiving immunotherapy; multiple recurrences might be a candidate predictor. More marker-driven prospective studies are warranted.
Topics: Brain Neoplasms; DNA Methylation; DNA Modification Methylases; Glioblastoma; Humans; Immunotherapy; Neoplasm Recurrence, Local; Prognosis
PubMed: 35822692
DOI: 10.1111/cns.13915 -
Briefings in Bioinformatics Jul 2022In recent years there has been a widespread interest in researching biomarkers of aging that could predict physiological vulnerability better than chronological age....
In recent years there has been a widespread interest in researching biomarkers of aging that could predict physiological vulnerability better than chronological age. Aging, in fact, is one of the most relevant risk factors for a wide range of maladies, and molecular surrogates of this phenotype could enable better patients stratification. Among the most promising of such biomarkers is DNA methylation-based biological age. Given the potential and variety of computational implementations (epigenetic clocks), we here present a systematic review of such clocks. Furthermore, we provide a large-scale performance comparison across different tissues and diseases in terms of age prediction accuracy and age acceleration, a measure of deviance from physiology. Our analysis offers both a state-of-the-art overview of the computational techniques developed so far and a heterogeneous picture of performances, which can be helpful in orienting future research.
Topics: Biomarkers; DNA Methylation; Epigenesis, Genetic; Epigenomics
PubMed: 35794713
DOI: 10.1093/bib/bbac274 -
Molecular Human Reproduction Jul 2022Polycystic ovary syndrome (PCOS) is often associated with aberrant DNA methylation. Despite the advances in diagnostics and treatment of PCOS, the pathophysiological... (Meta-Analysis)
Meta-Analysis
Polycystic ovary syndrome (PCOS) is often associated with aberrant DNA methylation. Despite the advances in diagnostics and treatment of PCOS, the pathophysiological mechanism remains unknown. Several genes are epigenetically dysregulated in PCOS and associated with pathological consequences of PCOS and metabolic comorbidities; however, the methylation status of specific genes and to what extent the genes are deregulated in terms of methylation pattern are unknown. This review aimed to analyse the existing data for specific genes and find conclusive evidence of their involvement in PCOS and associated risks. A comprehensive literature search was conducted in five electronic databases. The case-controlled clinical studies using both PCOS and healthy women and evaluating the methylation pattern without any treatment or intervention were included in the study. A random-effect model was used to extract the data for meta-analysis, and outcomes were expressed as standardized mean difference with a 95% CI. From 541 screened records, 41 studies were included in the review and 21 of them were used for meta-analysis of 20 genes. Meta-analysis revealed a significant global DNA hypomethylation in different tissues and peripheral blood of patients with PCOS compared to healthy controls. Specific gene methylation assessment revealed that genes associated with several functions were significantly hypomethylated and hypermethylated in patients with PCOS. This review provides conclusive evidence of epigenetic deregulation of specific genes in PCOS. These genes can potentially be used to develop diagnostic biomarkers or as targets for personalized therapy.
Topics: Case-Control Studies; DNA; DNA Methylation; Female; Genomics; Humans; Polycystic Ovary Syndrome
PubMed: 35789386
DOI: 10.1093/molehr/gaac024 -
Schizophrenia Research Aug 2022Evidence suggests that schizophrenia (SZ) is associated with accelerated biological aging. DNA methylation can be used as an indicator of biological aging by means of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Evidence suggests that schizophrenia (SZ) is associated with accelerated biological aging. DNA methylation can be used as an indicator of biological aging by means of epigenetic clock estimates.
OBJECTIVE
The aim of this systematic review and meta-analysis was to investigate the association between SZ and different epigenetic clocks.
METHODS
Search terms were applied in different databases: Embase, MEDLINE (EBSCO), Cochrane Central Register of Controlled Trials, PubMed, PsychINFO and Web of Science. To assess for risk of bias we utilized an adapted version of the Newcastle-Ottawa Scale. Meta-analyses were conducted using the random effects model and meta-regressions were used to assess factors associated with heterogeneity.
RESULTS
Eight studies were included (Controls, n = 3394; SZ subjects, n = 3096), which analyzed five different epigenetic clocks. Overall meta-analysis revealed no significant differences between SZ and controls on epigenetic aging (Standardized Mean Difference - SMD = -0.21; p = 0.13). However, epigenetic clock method was a significant moderator of heterogeneity (p = 0.004). Using Horvath's clock as reference, higher SMD's were found for PhenoAge and Intrinsic epigenetic age acceleration (IEAA) clocks. In a stratified meta-analysis restricted to the two clocks mentioned above, a significant accelerating effect was found in patients with SZ when compared to controls (SMD = 0.29; p = 0.003).
CONCLUSION
Our findings suggest that the method of epigenetic clocks is a critical factor associated with estimates of aging acceleration in SZ. However, more studies are needed to confirm these findings and in order to evaluate a possible minor effect in overall analysis.
Topics: Aging; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans; Schizophrenia
PubMed: 35780750
DOI: 10.1016/j.schres.2022.06.029 -
Epigenomics Jun 2022We systematically reviewed and evaluated current literature on alcohol consumption and DNA methylation (DNAm) at the genome-wide and probe-wise level in blood of... (Review)
Review
We systematically reviewed and evaluated current literature on alcohol consumption and DNA methylation (DNAm) at the genome-wide and probe-wise level in blood of adults. Five databases (PubMed, Embase, Web of Science, CINAHL and PsycInfo) were searched until 20 December 2020. Studies assessing the effect of alcohol dependence on DNAm were not eligible. 11 cross-sectional studies were included with 88 to 9643 participants. Overall, all studies had a risk of bias criteria unclear or unmet. Epigenome-wide association studies identified between 0 and 5458 differentially methylated positions, and 15 were observed in at least four studies. Potential methylation markers for alcohol consumption have been identified, but further validation in large cohorts is needed.
Topics: Adult; Alcohol Drinking; Alcoholism; Cross-Sectional Studies; DNA Methylation; Epigenesis, Genetic; Epigenome; Genome-Wide Association Study; Humans
PubMed: 35762294
DOI: 10.2217/epi-2022-0055 -
Contrast Media & Molecular Imaging 2022This study systematically reviewed the effect of DNA methylation in the promoter region of the coagulation factor vWF gene on the risk of unexplained recurrent... (Meta-Analysis)
Meta-Analysis
Correlation Analysis of DNA Methylation in the von Willebrand Factor Promoter Region and the Risk of Unexplained Recurrent Hemophilia: Systematic Review and Meta-Analysis.
This study systematically reviewed the effect of DNA methylation in the promoter region of the coagulation factor vWF gene on the risk of unexplained recurrent hemophilia. PubMed, Medline, Web of Science, and other computers were used to search the database, and the statistical randomized controlled trials of coagulation factor vWF in the risk analysis of unknown recurrent hemophilia were collected. The Cochrane systematic evaluation method was used to evaluate the quality of the included kinds of literature, and Revman5 software was used to sort out and analyze the kinds of literature. Meta-analysis showed that there was a statistical difference between the experimental group and the control group in case fatality rate (OR = 1.76, 95% CI (1.29, 2.39), =0.0003, = 0%, = 3.58), adverse events (OR = 2.38, 95% CI (1.65, 3.45), < 0.00001, = 0%, = 4.60), incidence of joint hemorrhage (OR = 2.52, 95% CI (1.62, 3.91), < 0.00001, = 0%, = 4.12), incidence of subcutaneous stasis (OR = 1.76, 95% CI (1.26, 2.45), =0.0009, = 5%, = 3.33), and hematoma volume (OR = 1.78, 95% CI (1.32, 2.40), =0.0001, = 23%, = 3.80). DNA methylation in the promoter region of the coagulation factor vWF gene was significantly associated with the risk of unexplained recurrent hemophilia. Whether demethylation can improve the bleeding index of patients with recurrent hemophilia remains to be further explored.
Topics: DNA Methylation; Hemophilia A; Humans; Promoter Regions, Genetic; von Willebrand Factor
PubMed: 35711531
DOI: 10.1155/2022/3977289