-
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 -
Placenta Nov 2020Pre-eclampsia (PE) is the major cause of fetal and maternal mortality and can be classified according to gestational age of onset into early-onset (EOPE, <34 weeks of... (Meta-Analysis)
Meta-Analysis
Pre-eclampsia (PE) is the major cause of fetal and maternal mortality and can be classified according to gestational age of onset into early-onset (EOPE, <34 weeks of gestation) and late- (LOPE, ≥34 weeks of gestation). DNA methylation (DNAm) may help to understand the abnormal placentation in PE. Therefore, we performed a systematic review to assess the role of global DNAm on pathophysiology of PE, focused on fetal and maternal tissues of placenta from pregnant with PE, including EOPE and LOPE. We searched the databases EMBASE, Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Scielo and Google Scholar, and followed the MOOSE guidelines. Moreover, we performed pathway analysis with the overlapping genes from the included studies. Twelve out of 24 included studies in the qualitative analysis considered the classification into EOPE and LOPE. We did not found heterogeneity in the criteria used for diagnosis of PE, and a few studies evaluated whether confounding factors would influence placental DNAm. Fourteen out of 24 included studies showed hypomethylation in placental tissue from pregnant with PE compared to controls. The differences in DNAm are specific to genes or differentially methylated regions, and more evident in EOPE and preterm PE compared to controls, rather than LOPE and term PE. The overlapping genes from included studies revealed pathways relevant to pathophysiology of PE. Our findings highlighted the heterogeneous results of the included studies, mainly focused on North America and China. Replication studies in different populations should use the same placental tissues, techniques to assess DNAm and pipelines for bioinformatic analysis.
Topics: DNA Methylation; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy
PubMed: 32942147
DOI: 10.1016/j.placenta.2020.09.004 -
Cancers Apr 2022Identification of non-metastatic colorectal cancer (CRC) patients with a high risk of recurrence after tumor resection is important to select patients who might benefit... (Review)
Review
Identification of non-metastatic colorectal cancer (CRC) patients with a high risk of recurrence after tumor resection is important to select patients who might benefit from adjuvant treatment. Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) analyses after surgery are promising biomarkers to predict recurrence in these patients. However, these analyses face several challenges and do not allow guidance of neoadjuvant treatment, which might become a novel standard option in colon cancer treatment. The prognostic value of cfDNA/ctDNA before surgery is unclear. This systematic review aims to provide an overview of publications in which the prognostic value of presurgery cfDNA/ctDNA in non-metastatic CRC patients was studied and is performed according to PRISMA guidelines. A total of 29 out of 1233 articles were included and categorized into three groups that reflect the type of approach: measurement of cfDNA, ctDNA somatic alterations, and ctDNA methylation. Overall, a clear association between presurgery cfDNA/ctDNA and the outcome was not observed, but large studies that primarily focus on the prognostic value of presurgery cfDNA/ctDNA are lacking. Designing and performing studies that focus on the value of presurgery cfDNA/ctDNA is needed, in addition to standardization in the reporting of cfDNA/ctDNA results according to existing guidelines to improve comparability and interpretation among studies.
PubMed: 35565347
DOI: 10.3390/cancers14092218 -
Cancers Mar 2021The objective of this systematic review is to summarize our current knowledge on the influence of miRNAs in the epigenetic deregulation of tumor-related genes in... (Review)
Review
The objective of this systematic review is to summarize our current knowledge on the influence of miRNAs in the epigenetic deregulation of tumor-related genes in endometrial cancer (EC). We conducted a literature search on the role of miRNAs in the epigenetic regulation of EC applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following terms were used: microRNA, miRNA, miR, endometrial cancer, endometrium, epigenetic, epimutation, hypermethylation, lynch, deacetylase, DICER, novel biomarker, histone, chromatin. The miRNAs were classified and are presented according to their function (tumor suppressor or onco-miRNA), their targets (when known), their expression levels in EC tissue vs the normal surrounding tissue, and the degree of DNA methylation in miRNA loci and CpG sites. Data were collected from 201 articles, including 190 original articles, published between November 1, 2008 and September 30, 2020 identifying 313 different miRNAs implicated in epigenetic regulation of EC. Overall, we identified a total of 148 miRNAs with decreased expression in EC, 140 miRNAs with increased expression in EC, and 22 miRNAs with discordant expression levels. The literature implicated different epigenetic phenomena including altered miRNA expression levels (miR-182, -230), changes in the methylation of miRNA loci (miR-34b, -129-2, -130a/b, -152, -200b, -625) and increased/decreased methylation of target genes (miR-30d,-191). This work provides an overview of all miRNAs reported to be involved in epigenetic regulation in EC including DNA methylation and RNA-associated silencing. These findings may contribute to novel strategies in diagnosis, risk assessment, and treatments aimed at miRNAs, their target genes or DNA methylation.
PubMed: 33800944
DOI: 10.3390/cancers13051137 -
Guidelines for pre-analytical conditions for assessing the methylation of circulating cell-free DNA.Clinical Epigenetics Oct 2021Methylation analysis of circulating cell-free DNA (cirDNA), as a liquid biopsy, has a significant potential to advance the detection, prognosis, and treatment of cancer,...
Methylation analysis of circulating cell-free DNA (cirDNA), as a liquid biopsy, has a significant potential to advance the detection, prognosis, and treatment of cancer, as well as many genetic disorders. The role of epigenetics in disease development has been reported in several hereditary disorders, and epigenetic modifications are regarded as one of the earliest and most significant genomic aberrations that arise during carcinogenesis. Liquid biopsy can be employed for the detection of these epigenetic biomarkers. It consists of isolation (pre-analytical) and detection (analytical) phases. The choice of pre-analytical variables comprising cirDNA extraction and bisulfite conversion methods can affect the identification of cirDNA methylation. Indeed, different techniques give a different return of cirDNA, which confirms the importance of pre-analytical procedures in clinical diagnostics. Although novel techniques have been developed for the simplification of methylation analysis, the process remains complex, as the steps of DNA extraction, bisulfite treatment, and methylation detection are each carried out separately. Recent studies have noted the absence of any standard method for the pre-analytical processing of methylated cirDNA. We have therefore conducted a comprehensive and systematic review of the important pre-analytical and analytical variables and the patient-related factors which form the basis of our guidelines for analyzing methylated cirDNA in liquid biopsy.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Cell-Free Nucleic Acids; DNA Methylation; Humans; Prognosis
PubMed: 34663458
DOI: 10.1186/s13148-021-01182-7 -
Therapeutic Advances in Medical Oncology 2022Testicular germ cell tumors (TGCTs) are the most common young male malignancy with a steadily rising incidence. Standard clinical practice is radical orchidectomy of... (Review)
Review
BACKGROUND
Testicular germ cell tumors (TGCTs) are the most common young male malignancy with a steadily rising incidence. Standard clinical practice is radical orchidectomy of suspicious lumps followed by histopathological diagnosis and tumor subtyping. This practice can lead to complications and quality of life issues for the patients. Liquid biopsies, especially cell-free DNA (cfDNA), promised to be true surrogates for tissue biopsies, which are considered dangerous to perform in cases of testicular tumors. In this study, we have performed a systematic review on the potential of cfDNA in TGCT patient management, its potential challenges in translation to clinical application and possible approaches in further research.
MATERIALS & METHODS
The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on EuropePMC and PUBMED electronic databases, with the last update being on October 21, 2021. Due to the high heterogeneity in identified research articles, we have performed an overview of their efficacy.
RESULTS
Eight original articles have been identified on cfDNA in TGCT patients published from 2004 to 2021, of which six had more than one TGCT patient enrolled and were included in the final analysis. Three studies investigated cfDNA methylation, one has investigated mutations in cfDNA, two have investigated cfDNA amount, and one has investigated cfDNA integrity in TGCT. The sensitivity of cfDNA for TGCT was found to be higher than in serum tumor markers and lower than miR-371a-3p, with comparable specificity. cfDNA methylation analysis has managed to accurately detect teratoma in TGCT patients.
CONCLUSION
Potential challenges in cfDNA application to TGCT patient management were identified. The challenges relating to the biology of TGCT with its low mutational burden and low cfDNA amounts in blood plasma make next-generation sequencing (NGS) methods especially challenging. We have also proposed possible approaches to help find clinical application, including a focus on cfDNA methylation analysis, and potentially solving the challenge of teratoma detection.
PubMed: 35656387
DOI: 10.1177/17588359221090365 -
Translational Cancer Research Jul 2022Although multiple gene promoter hypermethylation has been associated with gastric carcinogenesis, data on their specific relationship remains scant. We aimed to...
BACKGROUND
Although multiple gene promoter hypermethylation has been associated with gastric carcinogenesis, data on their specific relationship remains scant. We aimed to investigate the correlation between the status of multiple gene promoter methylation and gastric cancer (GC).
METHODS
We searched PubMed, EMBASE, CNKI, Wanfang, Cqvip and Cochrane Library up to May 2021. We systematically assessed the association between methylation status of the CpG islands and the risk of GC. We compared the incidence of DNA methylation between tumor and non-tumor tissues, and evaluated the clinicopathological significance of the DNA methylation in gastric carcinoma. The data was presented by an odds ratio (OR) with an accompanying 95% confidence interval (CI). We then generated forest plots calculated by fixed-effects or random-effects model.
RESULTS
This study enrolled a total of 201 studies (140 papers). Our analysis showed a higher frequency of methylation of the CpG islands in GC tissues compared to non-neoplastic tissues. Besides, the data demonstrated that polygene's aberrant promoter methylation might be linked to the initial development and progression of GC.
DISCUSSION
The genes with altered DNA methylation might serve as epigenetic biomarkers, providing a promising molecular diagnostic and prognostic tool for human GC. However, our findings need further evaluation in large randomized controlled trials.
PubMed: 35966315
DOI: 10.21037/tcr-22-372 -
Developmental Neurobiology Mar 2021Ash1l potentially contributes to neurodevelopmental diseases. Although specific Ash1l mutations are rare, they have led to informative studies in animal models that may... (Review)
Review
Ash1l potentially contributes to neurodevelopmental diseases. Although specific Ash1l mutations are rare, they have led to informative studies in animal models that may bring therapeutic advances. Ash1l is highly expressed in the brain and correlates with the neuropathology of Tourette syndrome (TS), autism spectrum disorder, and intellectual disability during development, implicating shared epigenetic factors and overlapping neuropathological mechanisms. Functional convergence of Ash1l generated several significant signaling pathways: chromatin remodeling and transcriptional regulation, protein synthesis and cellular metabolism, and synapse development and function. Here, we systematically review the literature on Ash1l, including its discovery, expression, function, regulation, implication in the nervous system, signaling pathway, mutations, and putative involvement in TS and other neurodevelopmental traits. Such findings highlight Ash1l pleiotropy and the necessity of transcending a single gene to complicated mechanisms of network convergence underlying these diseases. With the progress in functional genomic analysis (highlighted in this review), and although the importance and necessity of Ash1l becomes increasingly apparent in the medical field, further research is required to discover the precise function and molecular regulatory mechanisms related to Ash1l. Thus, a new perspective is proposed for basic scientific research and clinical interventions for cross-disorder diseases.
Topics: Animals; Autism Spectrum Disorder; DNA-Binding Proteins; Intellectual Disability; Neurodevelopmental Disorders; Tourette Syndrome
PubMed: 33258273
DOI: 10.1002/dneu.22795 -
Forensic Sciences Research 2021Epigenetic mechanisms are potential mediators of the physiological response to abuse by altering the genetic predisposition of the cellular response to the environment,... (Review)
Review
Epigenetic mechanisms are potential mediators of the physiological response to abuse by altering the genetic predisposition of the cellular response to the environment, leading to changes in the regulation of multiple organ systems. This study was established to review the epigenetic mechanisms associated with childhood abuse as well as the long-term determinants that these epigenetic changes may have on future illness. We retrospectively analysed the effect of exposure to adverse childhood experiences (ACEs, specifically those relating to childhood maltreatment) between the ages of 0 and 16 years on the human epigenome, as well as possible clinical associations. After meeting inclusion and exclusion criteria, 36 articles were included in this systematic review. Eight of these studies did not find a relationship between childhood maltreatment and DNA methylation. Of the remaining 28 studies, nine were genome-wide association studies, whereas the rest were candidate gene studies, mainly studying effects on neuroendocrine, serotoninergic and immunoregulatory systems. Meta-analysis of correlation coefficients from candidate gene studies estimated an association of childhood adversity and DNA methylation variation at = 0.291 ( < 0.0001), and meta-analysis of two epigenome-wide association studies (EWASs) identified 44 differentially methylated CpG sites. In conclusion, childhood maltreatment may mediate epigenetic mechanisms through DNA methylation, thereby affecting physiological responses and conferring a predisposition to an increased risk for psychopathology and forensic repercussions. Similar evidence for somatic illnesses is not yet available. KEY POINTSAdverse childhood experiences are associated with increased mortality partly explained by acquired epigenetic changesThere is a positive correlation between childhood abuse and DNA methylation at specific gene sitesThe cumulative effect of different types of childhood abuse and neglect may lead to changes in DNA methylationEpigenome changes associated with childhood abuse appear to be involved in the development of psychiatric illness in adulthoodStudying epigenetic changes may have important public health and forensic applications in the future.
PubMed: 34377567
DOI: 10.1080/20961790.2019.1641954