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European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
The World Journal of Men's Health Jul 2024The () gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on methylation pattern in spermatozoa of...
PURPOSE
The () gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters.
MATERIALS AND METHODS
This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included.
RESULTS
Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I²=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI -0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360).
CONCLUSIONS
Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART.
PubMed: 37853535
DOI: 10.5534/wjmh.230094 -
International Journal of Endocrinology 2023Promoter methylation of glutathione-S-transferase 1 (GSTP1) is related to the occurrence of prostate cancer (PCa), but reports are inconsistent about the accuracy of... (Review)
Review
BACKGROUND
Promoter methylation of glutathione-S-transferase 1 (GSTP1) is related to the occurrence of prostate cancer (PCa), but reports are inconsistent about the accuracy of GSTP1 promoter methylation in PCa diagnosis and prognosis. Therefore, we systematically evaluated the diagnostic and prognostic value of GSTP1 promoter methylation in PCa.
METHODS
The PubMed, EMBASE, Web of Science, and PMC databases were searched for all relevant studies from the date of inception to November 31, 2021. We compared differences in the incidence of GSTP1 promoter methylation in cfDNA between prostate cancer patients and controls. The odds ratio (OR) and hazard ratio (HR) were used as effect sizes, and the result of each effect size is expressed as a 95% confidence interval (95% CI).
RESULTS
Our meta-analysis showed that the combined sensitivity and specificity of GSTP1 promoter methylation in cfDNA for the diagnosis of prostate cancer were 0.37 (95% CI = 0.23, 0.53) and 0.97 (95% CI = 0.88, 0.99), respectively. The area under the curve (AUC) with 95% CI was 0.78 (95% CI = 0.75, 0.82). For prognostic variables, hypermethylation of GSTP1 was associated with shorter survival in PCa (HR = 2.57, 95% CI = 1.30, 5.10), with statistical significance in between-study heterogeneity ( = 72%, =0.006). The results of the subgroup analysis indicated that the heterogeneity of studies may be due to differences in the observed indicators.
CONCLUSIONS
The results of the meta-analysis substantiate the high specificity of promoter methylation of GSTP1 in cfDNA for the diagnosis of prostate cancer, and it may be used to more precisely evaluate the prognosis of patients with prostate cancer. It may be helpful for the early detection of prostate cancer, but it still must be combined with traditional prostate-specific antigen (PSA) or other methylated genes to accomplish this goal.
PubMed: 36747996
DOI: 10.1155/2023/7279243 -
Epigenetics Dec 2024Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health.... (Review)
Review
Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health. Micronutrients including folate, choline, and vitamin B provide methyl groups for the one-carbon metabolism and subsequent DNA methylation processes. Placental DNA methylation changes in response to one-carbon moieties hold potential targets to improve obstetrical care. We conducted a systematic review on the associations between one-carbon metabolism and human placental DNA methylation. We included 22 studies. Findings from clinical studies with minimal ErasmusAGE quality score 5/10 ( = 15) and studies ( = 3) are summarized for different one-carbon moieties. Next, results are discussed per study approach: (1) global DNA methylation ( = 9), (2) genome-wide analyses ( = 4), and (3) gene specific ( = 14). Generally, one-carbon moieties were not associated with global methylation, although conflicting outcomes were reported specifically for choline. Using genome-wide approaches, few differentially methylated sites associated with S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), or dietary patterns. Most studies taking a gene-specific approach indicated site-specific relationships depending on studied moiety and genomic region, specifically in genes involved in growth and development including , , and ; however, overlap between studies was low. Therefore, we recommend to further investigate the impact of an optimized one-carbon metabolism on DNA methylation and lifelong health.
Topics: Female; Humans; Pregnancy; DNA Methylation; Placenta; Genome-Wide Association Study; Folic Acid; S-Adenosylmethionine; Choline; Carbon
PubMed: 38484284
DOI: 10.1080/15592294.2024.2318516 -
International Journal of Molecular... Aug 2023This review explores the emerging role of hydrogen sulfide (HS) in modulating epigenetic mechanisms involved in neurodegenerative diseases. Accumulating evidence has... (Review)
Review
This review explores the emerging role of hydrogen sulfide (HS) in modulating epigenetic mechanisms involved in neurodegenerative diseases. Accumulating evidence has begun to elucidate the multifaceted ways in which HS influences the epigenetic landscape and, subsequently, the progression of various neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's disease. HS can modulate key components of the epigenetic machinery, such as DNA methylation, histone modifications, and non-coding RNAs, impacting gene expression and cellular functions relevant to neuronal survival, inflammation, and synaptic plasticity. We synthesize recent research that positions HS as an essential player within this intricate network, with the potential to open new therapeutic avenues for these currently incurable conditions. Despite significant progress, there remains a considerable gap in our understanding of the precise molecular mechanisms and the potential therapeutic implications of modulating HS levels or its downstream targets. We conclude by identifying future directions for research aimed at exploiting the therapeutic potential of HS in neurodegenerative diseases.
Topics: Humans; Hydrogen Sulfide; Epigenesis, Genetic; Neurodegenerative Diseases; Huntington Disease; Cell Survival
PubMed: 37628735
DOI: 10.3390/ijms241612555 -
Epigenetics Apr 2022When used during pregnancy, analgesics and psychotropics pass the placenta to enter the foetal circulation and may induce epigenetic modifications. Where such...
When used during pregnancy, analgesics and psychotropics pass the placenta to enter the foetal circulation and may induce epigenetic modifications. Where such modifications occur and whether they disrupt normal foetal developme nt, are currently unanswered questions. This field of prenatal pharmacoepigenetics has received increasing attention, with several studies reporting associations between medication exposure and offspring epigenetic outcomes. Nevertheless, no recent systematic review of the literature is available. Therefore, the objectives of this review were to (i) provide an overview of the literature on the association of prenatal exposure to psychotropics a nd analgesics with epigenetic outcomes, and (ii) suggest recommendations for future studies within prenatal pharmacoepigenetics. We performed systematic literature searches in five databases. The eligible studies assessed human prenatal exposure to psychotropics or analgesics, with epigenetic analyses of offspring tissue as an outcome. We identified 18 eligible studies including 4,419 neonates exposed to either antidepressants, antiepileptic drugs, paracetamol, acetylsalicylic acid, or methadone. The epigenetic outcome in all studies was DNA methylation in cord blood, placental tissue or buccal cells. Although most studies found significant differences in DNA methylation upon medication exposure, almost no differences were persistent across studies for similar medications and sequencing methods. The reviewed studies were challenging to compare due to poor transparency in reporting, and heterogeneous methodology, design, genome coverage, and statistical modelling. We propose 10 recommendations for future prenatal pharmacoepigenetic studies considering both epidemiological and epigenetic perspectives. These recommendations may improve the quality, comparability, and clinical relevance of such studies. PROSPERO registration ID: CRD42020166675.
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Female; Humans; Infant, Newborn; Mouth Mucosa; Placenta; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 33926354
DOI: 10.1080/15592294.2021.1903376 -
Pancreatology : Official Journal of the... Nov 2022Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice.
METHODS
A systematic literature search was performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL and Web of Science for studies concerning the diagnostic performance of DNA alterations in pancreatic juice to differentiate patients with high-grade dysplasia or pancreatic cancer from controls. Study quality was assessed using QUADAS-2. The pooled prevalence, sensitivity, specificity and diagnostic odds ratio were calculated.
RESULTS
Studies mostly concerned cell-free DNA mutations (32 studies: 939 cases, 1678 controls) and methylation patterns (14 studies: 579 cases, 467 controls). KRAS, TP53, CDKN2A, GNAS and SMAD4 mutations were evaluated most. Of these, TP53 had the highest diagnostic performance with a pooled sensitivity of 42% (95% CI: 31-54%), specificity of 98% (95%-CI: 92%-100%) and diagnostic odds ratio of 36 (95% CI: 9-133). Of DNA methylation patterns, hypermethylation of CDKN2A, NPTX2 and ppENK were studied most. Hypermethylation of NPTX2 performed best with a sensitivity of 39-70% and specificity of 94-100% for distinguishing pancreatic cancer from controls.
CONCLUSIONS
This meta-analysis shows that, in pancreatic juice, the presence of distinct DNA mutations (TP53, SMAD4 or CDKN2A) and NPTX2 hypermethylation have a high specificity (close to 100%) for the presence of high-grade dysplasia or pancreatic cancer. However, the sensitivity of these DNA alterations is poor to moderate, yet may increase if they are combined in a panel.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Early Detection of Cancer; Mutation; Pancreatic Juice; Pancreatic Neoplasms
PubMed: 35864067
DOI: 10.1016/j.pan.2022.06.260 -
British Medical Bulletin Oct 2020Tendon is a composite material with a well-ordered hierarchical structure exhibiting viscoelastic properties designed to transfer force. It is recognized that the...
INTRODUCTION
Tendon is a composite material with a well-ordered hierarchical structure exhibiting viscoelastic properties designed to transfer force. It is recognized that the incidence of tendon injury increases with age, suggesting a deterioration in homeostatic mechanisms or reparative processes. This review summarizes epigenetic mechanisms identified in ageing healthy tendon.
SOURCES OF DATA
We searched multiple databases to produce a systematic review on the role of epigenetic mechanisms in tendon ageing.
AREAS OF AGREEMENT
Epigenetic mechanisms are important in predisposing ageing tendon to injury.
AREAS OF CONTROVERSY
The relative importance of epigenetic mechanisms are unknown in terms of promoting healthy ageing. It is also unknown whether these changes represent protective mechanisms to function or predispose to pathology.
GROWING POINT
Epigenetic markers in ageing tendon, which are under-researched including genome-wide chromatin accessibility, should be investigated.
AREAS TIMELY FOR DEVELOPING RESEARCH
Metanalysis through integration of multiple datasets and platforms will enable a holistic understanding of the epigenome in ageing and its relevance to disease.
Topics: Aging; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans; Tendons
PubMed: 32827252
DOI: 10.1093/bmb/ldaa023 -
Epigenetics Dec 2022The aim of the present systematic review was to critically analyse the relationship between tumour suppressor genes (TSGs) promoter methylation, a potent mechanism of... (Meta-Analysis)
Meta-Analysis Review
The aim of the present systematic review was to critically analyse the relationship between tumour suppressor genes (TSGs) promoter methylation, a potent mechanism of gene silencing, and the development of salivary gland tumours, as well as the possible effect on clinical/histological characteristics. Review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (registration ID CRD42020218511). A comprehensive search of Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials was performed utilizing relevant key terms, supplemented by a search of grey literature. Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used for the quality assessment of included studies. Sixteen cross-sectional and 12 case-control studies were included in the review, predominantly dealing with methylation in TSGs related to DNA repair, cell cycle, and cell growth regulation and differentiation. Quantitative synthesis could be performed on P16 (inhibitor of cyclin-dependent kinase 4a), RASSF1A (Ras association domain family 1 isoform A) and MGMT (O6-methylguanine DNA methyltransferase) genes only. It showed that P16 and RASSF1A genes were more frequently methylated in salivary gland tumours compared to controls ( = .0002 and < .0001, respectively), while no significant difference was observed for MGMT. Additionally, P16 did not appear to be related to malignant transformation of pleomorphic adenomas ( = .330). In conclusion, TSG methylation is involved in salivary gland tumour pathogenesis and several genes might play a considerable role. Further studies are needed for a better understanding of complex epigenetic deregulation during salivary gland tumour development and progression.
Topics: Humans; Genes, Tumor Suppressor; DNA Methylation; Cross-Sectional Studies; Salivary Gland Neoplasms; Cyclin-Dependent Kinases; DNA
PubMed: 35287544
DOI: 10.1080/15592294.2022.2052426 -
Noise & Health 2020Noise-induced hearing loss (NIHL) is one of the leading causes of acquired sensorineural hearing loss. However, molecular mechanisms responsible for its pathogenesis...
BACKGROUND
Noise-induced hearing loss (NIHL) is one of the leading causes of acquired sensorineural hearing loss. However, molecular mechanisms responsible for its pathogenesis remain to be elucidated. Epigenetic changes, i.e. DNA methylation, histone and microRNA expression modifications may function as a link between noise exposure and hearing loss. Therefore, the aim of the present review was to assess whether epigenetic alterations may serve as biomarkers of noise exposure or early effect.
MATERIALS AND METHODS
A systematic review of studies available in Pubmed, Scopus, and ISI Web of Science databases was performed.
RESULTS
Noise exposure was able to induce alterations in DNA methylation levels in workers and animal models, resulting in expression changes of genes related to hearing loss and also to extra-auditory effects. Differently expressed microRNAs were determined in NIHL workers compared to noise-exposed subjects with normal hearing, supporting their possible role as biomarkers of effect. Acoustic trauma affected histon acethylation and methylation levels in animals, suggesting their influence in the pathogenesis of acute noise-induced damage and their role as targets for potential therapeutic treatments.
CONCLUSIONS
Although preliminary data suggest a relationship between noise and epigenetic effects, the limited number of studies, their different methodologies and the lack of adequate characterization of acoustic insults prevent definite conclusions. In this context, further research aimed to define the epigenetic impact of workplace noise exposure and the role of such alterations in predicting hearing loss may be important for the adoption of correct risk assessment and management strategies in occupational settings.
Topics: Animals; DNA Methylation; Environmental Exposure; Epigenesis, Genetic; Genetic Markers; Hearing Loss, Noise-Induced; Histones; Humans; MicroRNAs; Noise; Occupational Diseases; Risk Assessment
PubMed: 33402608
DOI: 10.4103/nah.NAH_17_20