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Biology Mar 2023Endometriosis is an inflammatory chronic systemic disease resulting in pelvic pain and infertility. However, despite a high prevalence of endometriosis, disease... (Review)
Review
Endometriosis is an inflammatory chronic systemic disease resulting in pelvic pain and infertility. However, despite a high prevalence of endometriosis, disease identification is still insufficient, and a high percentage of misdiagnosing was observed. Hence, a comprehensive study needs to be done to improve our understanding of the pathogenesis of endometriosis. Aberrant hypermethylation of HOXA10 has been reported to play a role in endometriosis. Thus, a comprehensive literature search was conducted to identify the DNA methylation level of HOXA10 among endometriosis patients across populations. The literature search was done using PubMed, Scopus, EBSCOhost, and Science Direct applying (HOXA10 OR "homeobox A10" OR "HOXA-10" OR HOX1) AND ("DNA methylation" OR methylation) AND (endometriosis OR endometrioma) as keywords. From 491 retrieved studies, five original articles investigating the DNA methylation level of HOXA10 from endometrium tissues among endometriosis women were included. All five included studies were classified as high-quality studies. High HOXA10 DNA methylation level was observed in the endometrium tissue of women with endometriosis in all the included studies. The secretory phase was identified as the best sampling time for HOXA10 DNA methylation study in endometriosis, and the most studied DNA methylation site is the promoter region of the HOXA10. However, more studies are needed to expose the HOXA10 mechanism in the pathogenesis of endometriosis.
PubMed: 36979165
DOI: 10.3390/biology12030474 -
International Journal of Surgery... Apr 2023Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early...
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early detection and intervention can effectively improve the survival rate and quality of life. Although colonoscopy can detect and diagnose CRC, it is unsuitable for CRC screening in average-risk populations. Some commercial kits based on DNA mutation or methylation are approved for screening, but the low sensitivity for advanced adenoma or early-stage CRC would limit the applications.
MAIN RESULTS
Recently, researchers have focused on developing noninvasive or minimally invasive, easily accessible biomarkers with higher sensitivity and accuracy for CRC screening. Numerous reports describe advances in biomarkers, including DNA mutations and methylation, mRNA and miRNA, gut microbes, and metabolites, as well as low-throughput multiomics panels. In small cohorts, the specificity and sensitivity improved when fecal immunochemical testing combined with other biomarkers; further verification in large cohorts is expected. In addition, the continuous improvement of laboratory technology has also improved the sensitivity of detection technology, such as PCR, and the application of CRISPR/Cas technology. Besides, artificial intelligence has extensively promoted the mining of biomarkers. Machine learning was performed to construct a diagnosis model for CRC screening based on the cfDNA fragment features from whole-genome sequencing data. In another study, multiomics markers, including cfDNA, epigenetic, and protein signals, were also discovered by machine learning. Finally, advancements in sensor technology promote the applicability of volatile organic compounds in CRC early detection.
CONCLUSION
Here, the authors review advances in early detection and screening of CRC based on different biomarker types. Most studies reported optimistic findings based on preliminary research, and prospective clinical studies are ongoing. These promising biomarkers are expected to more accurately identify early-stage patients with CRC and be applied in the future.
Topics: Humans; Prospective Studies; Artificial Intelligence; Quality of Life; Biomarkers, Tumor; Early Detection of Cancer; DNA; Cell-Free Nucleic Acids; Colorectal Neoplasms
PubMed: 36974713
DOI: 10.1097/JS9.0000000000000260 -
Phenomics (Cham, Switzerland) Apr 2022Increasing evidence has demonstrated that abnormal epigenetic modifications are strongly related to cancer initiation. Thus, sensitive and specific detection of... (Review)
Review
Increasing evidence has demonstrated that abnormal epigenetic modifications are strongly related to cancer initiation. Thus, sensitive and specific detection of epigenetic modifications could markedly improve biological investigations and cancer precision medicine. A rapid development of molecular imaging approaches for the diagnosis and prognosis of cancer has been observed during the past few years. Various biomarkers unique to epigenetic modifications and targeted imaging probes have been characterized and used to discriminate cancer from healthy tissues, as well as evaluate therapeutic responses. In this study, we summarize the latest studies associated with optical molecular imaging of epigenetic modification targets, such as those involving DNA methylation, histone modification, noncoding RNA regulation, and chromosome remodeling, and further review their clinical application on cancer diagnosis and treatment. Lastly, we further propose the future directions for precision imaging of epigenetic modification in cancer. Supported by promising clinical and preclinical studies associated with optical molecular imaging technology and epigenetic drugs, the central role of epigenetics in cancer should be increasingly recognized and accepted.
PubMed: 36939779
DOI: 10.1007/s43657-021-00041-y -
World Journal of Gastroenterology Feb 2023Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified...
BACKGROUND
Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear.
AIM
To improve the current understanding of the molecular basis of CRC
METHODS
A literature search in the Medline database, (https:// www.referencecitationanalysis.com/), and manual reference screening were performed to identify observational studies published from inception to May 2022.
RESULTS
A total of fourteen case-control studies and five cohort studies were identified. These studies included information on dietary methyl donors, dietary components that potentially modulate the bioavailability of methyl groups, genetic variants of methyl metabolizing enzymes, and/or markers of CpG island methylator phenotype and/or microsatellite instability, and their possible interactions on CRC risk.
CONCLUSION
Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms, methyl donor nutrients (such as folate) and alcohol on CRC risk. Moreover, vitamin B, niacin, and alcohol may affect CRC risk through not only genetic but also epigenetic regulation. Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.
Topics: Humans; Epigenesis, Genetic; Colorectal Neoplasms; Folic Acid; DNA Methylation; Microsatellite Instability; Nutrients; CpG Islands
PubMed: 36926668
DOI: 10.3748/wjg.v29.i7.1219 -
Sultan Qaboos University Medical Journal Feb 2023This systematic review and meta-analysis aimed to assess the cytotoxic and genotoxic impacts of waterpipe smoking on oral health. The databases MEDLINE, Cochrane Library... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to assess the cytotoxic and genotoxic impacts of waterpipe smoking on oral health. The databases MEDLINE, Cochrane Library and Dimensions were searched to find studies evaluating whether waterpipe smokers exhibited any cytotoxic or genotoxic effects on their oral cells compared to non-smokers, with regard to mouth neoplasms. Particularly, changes in DNA methylation and p53 expression were assessed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted for the systematic review. Review Manager was utilised for statistical analysis with a significance level at <0.05. To assess the grades of the included articles, a risk of bias analysis was summarised. A forest plot, including some of the included articles included, was created regarding the different grades. A total of 20 studies were included in this review. The results showed that waterpipe smoking has cytotoxic and genotoxic effects on oral cells, with a risk difference of 0.16. Although the published articles are few in number, all confirm the devastating effects of waterpipe smoking related to the carcinogenicity. Waterpipe smoking is harmful to oral health. It causes a series of detrimental cellular and genetic modifications such as acanthosis, epithelial dysplasia and hyperparakeratosis. In addition, waterpipe smoke contains several carcinogenic compounds. As it releases many harmful organic compounds, waterpipe smoking increases the incidence of oral cancer.
Topics: Humans; Oral Health; Water Pipe Smoking; Antineoplastic Agents; Mouth Neoplasms; DNA Damage
PubMed: 36865434
DOI: 10.18295/squmj.6.2022.043 -
RMD Open Mar 2023To systematically review the literature for assay methods that aim to evaluate type I interferon (IFN-I) pathway activation and to harmonise-related terminology.
OBJECTIVES
To systematically review the literature for assay methods that aim to evaluate type I interferon (IFN-I) pathway activation and to harmonise-related terminology.
METHODS
Three databases were searched for reports of IFN-I and rheumatic musculoskeletal diseases. Information about the performance metrics of assays measuring IFN-I and measures of truth were extracted and summarised. A EULAR task force panel assessed feasibility and developed consensus terminology.
RESULTS
Of 10 037 abstracts, 276 fulfilled eligibility criteria for data extraction. Some reported more than one technique to measure IFN-I pathway activation. Hence, 276 papers generated data on 412 methods. IFN-I pathway activation was measured using: qPCR (n=121), immunoassays (n=101), microarray (n=69), reporter cell assay (n=38), DNA methylation (n=14), flow cytometry (n=14), cytopathic effect assay (n=11), RNA sequencing (n=9), plaque reduction assay (n=8), Nanostring (n=5), bisulphite sequencing (n=3). Principles of each assay are summarised for content validity. Concurrent validity (correlation with other IFN assays) was presented for n=150/412 assays. Reliability data were variable and provided for 13 assays. Gene expression and immunoassays were considered most feasible. Consensus terminology to define different aspects of IFN-I research and practice was produced.
CONCLUSIONS
Diverse methods have been reported as IFN-I assays and these differ in what elements or aspects of IFN-I pathway activation they measure and how. No 'gold standard' represents the entirety of the IFN pathway, some may not be specific for IFN-I. Data on reliability or comparing assays were limited, and feasibility is a challenge for many assays. Consensus terminology should improve consistency of reporting.
Topics: Humans; Interferon Type I; Reproducibility of Results; Musculoskeletal Diseases; Rheumatic Diseases; Advisory Committees
PubMed: 36863752
DOI: 10.1136/rmdopen-2022-002876 -
Pathogens (Basel, Switzerland) Feb 2023Interest in host epigenetic changes during apicomplexan infections increased in the last decade, mainly due to the emergence of new therapies directed to these... (Review)
Review
Interest in host epigenetic changes during apicomplexan infections increased in the last decade, mainly due to the emergence of new therapies directed to these alterations. This review aims to carry out a bibliometric analysis of the publications related to host epigenetic changes during apicomplexan infections and to summarize the main studied pathways in this context, pointing out those that represent putative drug targets. We used four databases for the article search. After screening, 116 studies were included. The bibliometric analysis revealed that the USA and China had the highest number of relevant publications. The evaluation of the selected studies revealed that was considered in most of the studies, non-coding RNA was the most frequently reported epigenetic event, and host defense was the most explored pathway. These findings were reinforced by an analysis of the co-occurrence of keywords. Even though we present putative targets for repurposing epidrugs and ncRNA-based drugs in apicomplexan infections, we understand that more detailed knowledge of the hosts' epigenetic pathways is still needed before establishing a definitive drug target.
PubMed: 36839571
DOI: 10.3390/pathogens12020299 -
Genes Feb 2023Chronic pain represents a major global health issue in terms of psycho-physiological, therapeutic, and economic burden, not limited to adults but also to the pediatric... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Chronic pain represents a major global health issue in terms of psycho-physiological, therapeutic, and economic burden, not limited to adults but also to the pediatric age. Despite its great impact, its molecular mechanisms have still not been completely unraveled. Focusing on the impact of epigenetics in the pain complex trait, we assessed the association between chronic pain and the methylation pattern of TRPA1, a key gene related to pain sensitivity.
METHODS
We conducted a systematic review retrieving articles from three different databases. After deduplication, 431 items were subjected to manual screening, and then 61 articles were selected and screened again. Of these, only six were maintained for meta-analysis and analyzed using specific R packages.
RESULTS
Six articles were divided into two groups (group 1: comparison of mean methylation levels between healthy subjects and patients with chronic pain; group 2: correlation between mean methylation levels and pain sensation). A non-significant mean difference was obtained from the analysis of group 1 with a value of 3.97 (95% C.I. -7.79; 15.73). Analysis of group 2 showed a high level of variability between studies (correlation = 0.35, 95% C.I. -0.12; 0.82) due to their heterogeneity (I = 97%, < 0.01).
CONCLUSIONS
Despite the high variability observed in the different studies analyzed, our results suggest that hypermethylation and increased pain sensitivity could be connected, possibly due to the variation of TRPA1 expression.
Topics: Adult; Child; Humans; Ankyrins; Chronic Pain; DNA Methylation; Epigenesis, Genetic; TRPA1 Cation Channel
PubMed: 36833338
DOI: 10.3390/genes14020411 -
Biomedicines Feb 2023A small subset of people with nephrotic syndrome (NS) have genetically driven disease. However, the disease mechanisms for the remaining majority are unknown. Epigenetic... (Review)
Review
A small subset of people with nephrotic syndrome (NS) have genetically driven disease. However, the disease mechanisms for the remaining majority are unknown. Epigenetic marks are reversible but stable regulators of gene expression with utility as biomarkers and therapeutic targets. We aimed to identify and assess all published human studies of epigenetic mechanisms in NS. PubMed (MEDLINE) and Embase were searched for original research articles examining any epigenetic mechanism in samples collected from people with steroid resistant NS, steroid sensitive NS, focal segmental glomerulosclerosis or minimal change disease. Study quality was assessed by using the Joanna Briggs Institute critical appraisal tools. Forty-nine studies met our inclusion criteria. The majority of these examined micro-RNAs ( = 35, 71%). Study quality was low, with only 23 deemed higher quality, and most of these included fewer than 100 patients and failed to validate findings in a second cohort. However, there were some promising concordant results between the studies; higher levels of serum miR-191 and miR-30c, and urinary miR-23b-3p and miR-30a-5p were observed in NS compared to controls. We have identified that the epigenome, particularly DNA methylation and histone modifications, has been understudied in NS. Large clinical studies, which utilise the latest high-throughput technologies and analytical pipelines, should focus on addressing this critical gap in the literature.
PubMed: 36831050
DOI: 10.3390/biomedicines11020514 -
Medicine Feb 2023An increasing number of studies have shown the potential diagnostic value of cell-free DNA (cfDNA) as a new biomarker in the management of thyroid cancer (TC); however,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
An increasing number of studies have shown the potential diagnostic value of cell-free DNA (cfDNA) as a new biomarker in the management of thyroid cancer (TC); however, the accuracy of research results is inconsistent. This meta-analysis is the first to synthesize published results and evaluate the application value of circulating cfDNA in the diagnosis of TC.
METHODS
A search strategy was developed according to PICO (P: Patient; I: Intervention; C: Comparison; O: Outcome) principles. We searched 5 databases until October 2022. Original studies that examined cfDNA for the diagnosis of TC and used pathology as the gold standard were included in this meta-analysis. A random-effects model was used to pool the data extracted from individual studies, including the number of patients and the numbers of true positives, false positives, true negatives, and false negatives.
RESULTS
A total of 622 patients with TC, 547 patients with benign thyroid nodules, and 98 healthy individuals were included in 20 studies reported in 14 articles. The types of cfDNA included in the research include specific mutations of cfDNA, methylation of cfDNA, the content of cfDNA, and cfDNA index. After rigorous statistical analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.76 (95% confidence interval [CI] 0.62-0.85), 0.87 (95% CI 0.78-0.93), 5.08 (95% CI 3.3-10.3), 0.28 (95% CI 0.17-0.46), 21 (95% CI 9-49), and 0.89 (95% CI 0.86-0.91), respectively. The meta-regression results showed that the number of cfDNAs, cfDNA methylation status, and sample size were the sources of heterogeneity in the specificity of the study. A subgroup analysis showed that the quantitative analysis group (cfDNA level) had a higher diagnostic accuracy than that of the qualitative analysis group (cfDNA methylation, mutation, or integrity index), with a sensitivity of 0.84, specificity of 0.89, and area under the curve of 0.91.
CONCLUSIONS
The results of this meta-analysis suggest that cfDNA has value as an adjunct for the diagnosis of TC. Quantitative detection of cfDNA can achieve relatively high diagnostic accuracy. However, due to heterogeneity, the test results based on cfDNA for TC should be interpreted with caution.
Topics: Humans; Cell-Free Nucleic Acids; ROC Curve; Biomarkers, Tumor; Mutation; Thyroid Neoplasms; Sensitivity and Specificity
PubMed: 36800605
DOI: 10.1097/MD.0000000000032928