Clinical Epigenetics最新文献

{"title":"Targeting PRMT1-mediated methylation of TAF15 to protect against myocardial infarction by inhibiting ferroptosis via the GPX4/NRF2 pathway.","authors":"Guanshen Huang, Liwei He, Bishan Liang, Mingjian Gao, Jianming Huang, Hao Xia, Xinyu Li, Hai Li, Yunjun Ruan","doi":"10.1186/s13148-025-01935-8","DOIUrl":"10.1186/s13148-025-01935-8","url":null,"abstract":"<p><strong>Background: </strong>Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. Ferroptosis, an iron-dependent form of regulated cell death, plays a crucial role in AMI progression. However, the molecular mechanisms regulating ferroptosis in AMI remain poorly understood. This study aims to investigate the role and potential regulatory mechanism of TAF15 in AMI.</p><p><strong>Methods: </strong>Bioinformatics analysis of gene expression datasets was conducted to identify differentially expressed genes in AMI samples. TAF15 expression was evaluated in clinical AMI patient blood samples, ischemia/reperfusion (I/R)-treated HL-1 cardiomyocytes, and myocardial tissues from the AMI mouse model using qRT-PCR and Western blot analyses. Gain- and loss-of-function experiments were performed to assess the effects of TAF15 and PRMT1 on myocardial injury, oxidative stress, and ferroptosis markers (Fe²⁺, MDA, GSH, GPX4, ROS) using electrocardiography, histopathology, CCK-8, EdU, TUNEL, ELISA, flow cytometry, qRT-PCR, and Western blot assays. Mechanistic studies, including luciferase reporter assays, chromatin immunoprecipitation (ChIP-qPCR), and bisulfite sequencing, were conducted to examine PRMT1-mediated TAF15 methylation and its regulatory effects.</p><p><strong>Results: </strong>TAF15 was significantly downregulated in AMI, as observed in patient samples and experimental models. Functionally, TAF15 overexpression significantly improved myocardial function by inhibiting ferroptosis. Notably, TAF15 overexpression restored GPX4 and NRF2 expression, reduced Fe²⁺ accumulation and lipid peroxidation (MDA levels), and increased GSH levels in both HL-1 cardiomyocytes and AMI mouse model. Mechanistic investigations revealed that TAF15 interacted with NRF2, enhancing TAF15 transcription and subsequently activating the GPX4/NRF2 axis, which protects against ferroptosis-induced cardiomyocyte death. Additionally, PRMT1 negatively regulated TAF15 via hypermethylation. PRMT1 knockdown significantly upregulated TAF15 expression, leading to reduced ferroptosis and improved cardiac function.</p><p><strong>Conclusions: </strong>This study establishes TAF15 as a novel regulator of ferroptosis in AMI, activating the GPX4/NRF2 pathway to mitigate oxidative stress and myocardial injury. Furthermore, PRMT1-mediated TAF15 hypermethylation promotes ferroptosis, thereby exacerbating myocardial damage. These findings suggest that targeting the PRMT1/TAF15/GPX4-NRF2 axis represents a promising therapeutic strategy for AMI treatment by inhibiting ferroptotic cell death and improving cardiac function.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"129"},"PeriodicalIF":4.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring breast cancer progression through circulating methylated GCM2 and TMEM240 detection.","authors":"Chin-Sheng Hung, Hsieh-Tsung Shen, Pei-Yu Wang, Chih-Ming Su, Wei-Wen Hsu, Kuan-Yu Chien, Cai-Sia Han, Li-Min Liao, Ruo-Kai Lin","doi":"10.1186/s13148-025-01939-4","DOIUrl":"10.1186/s13148-025-01939-4","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths in women worldwide. Approximately 20-30% of women diagnosed with early-stage breast cancer eventually develop metastatic disease. Current biomarkers, such as CA15-3 and CEA, detect metastasis in only 60-80% of cases, underscoring the need for improved diagnostic tools. This study investigates the potential of circulating methylated GCM2 and TMEM240 as biomarkers for noninvasive monitoring of breast cancer progression.</p><p><strong>Methods: </strong>In a prospective study conducted in Taiwan, 396 patients were enrolled, alongside a retrospective study of 134 plasma samples from Western populations. cfDNA was extracted, subjected to sodium bisulfite conversion, and the methylation levels of GCM2 and TMEM240 were measured using QMSP. Monte Carlo analysis assigned 70% of the dataset to a training set and 30% to a validation set, repeated 1000 times. Performance metrics such as sensitivity, specificity, and accuracy were averaged to ensure robustness, supporting the use of combined GCM2 and TMEM240 for monitoring treatment response and tumor burden.</p><p><strong>Results: </strong>The training set, consisting of 166 breast cancer patients (13.3% with recurrence or metastasis), was utilized to establish the biomarker detection cutoff. Validation in a separate cohort of 325 patients (20% with recurrence or metastasis) demonstrated superior performance compared to CA15-3 and CEA, achieving 95.1% accuracy, 89.4% sensitivity, 96.5% specificity, 86.8% positive predictive value (PPV), and 97.3% negative predictive value (NPV). Monte Carlo analysis of the training data revealed an average sensitivity of 95.7%, specificity of 90.3%, and accuracy of 91.5%, while validation data achieved 92.8% sensitivity, 89.5% specificity, and 90.3% accuracy across 1000 replicates. Positive cases were significantly associated with late-stage disease (P < 0.001), larger tumors (P = 0.002), distant metastasis (P < 0.001), and disease progression (P < 0.001). For monitoring treatment response and tumor burden, decreased methylation levels were observed in patients responding well to treatment, whereas increased levels were noted in cases of cancer progression or prior to metastasis.</p><p><strong>Conclusions: </strong>Overall, detecting methylated GCM2 and TMEM240 in plasma offers a novel, accurate, and noninvasive method for monitoring breast cancer progression.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"128"},"PeriodicalIF":4.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation in normal-appearing tissue associated with prostate cancer recurrence and metastasis.","authors":"Christine Aaserød Pedersen, Thomas Fleischer, Maximilian Wess, Elise Midtbust, Maria K Andersen, Trond Viset, Øystein Størkersen, Morten B Rye, May-Britt Tessem","doi":"10.1186/s13148-025-01932-x","DOIUrl":"10.1186/s13148-025-01932-x","url":null,"abstract":"<p><p>There is a need for more precise biomarkers and understanding on the development of aggressive prostate cancer. In this study, we analyzed DNA methylation in 64 prostate cancer tissue samples, using tissue from radical prostatectomy patients (n = 16) with up to 16 years of clinical follow-up. We used several samples from each patient including both normal and cancer tissue to study DNA methylation patterns in relation to aggressiveness measured by follow-up data of biochemical recurrence and metastasis status as clinical endpoints. We identified differentially methylated CpGs associated with recurrence and metastasis, regardless of whether the tissue was normal, cancer-adjacent normal, or cancer. The identified CpG sites were over-represented in promoter regions and transcription factor binding regions, suggesting their influence on gene expression regulation. They further exhibited low intrapatient heterogeneity both between normal, normal adjacent, and cancer tissue, making them favorable as potential biomarkers for aggressive prostate cancer. However, validation of a subset of these CpGs in an external dataset was unsuccessful.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"127"},"PeriodicalIF":4.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted regulation of the HOX cluster and its implications in oral cancer.","authors":"Kanaka Sai Ram Padam, Keith D Hunter, Raghu Radhakrishnan","doi":"10.1186/s13148-025-01933-w","DOIUrl":"10.1186/s13148-025-01933-w","url":null,"abstract":"<p><strong>Background: </strong>The hypothesis that aberrant expression of homeobox (HOX) transcription factors contributes to oral cancer progression is gaining prominence. However, the mechanism of regulation involved in the clustered dysregulation of HOX clusters is not clearly known.</p><p><strong>Results: </strong>Our findings revealed that HOXA and HOXB clusters showed significant locus-specific CpG methylation changes compared with the HOXC and HOXD clusters. The constitutively unmethylated regions identified in the HOXA1, HOXA11, HOXB5, HOXB6, HOXB9, HOXC5, HOXC10 and HOXC11 genes may be associated with open chromatin-mediated gene regulation. The methylation of CpG loci within the intron of HOXB9 may serve as a potential marker for distinguishing patients with premalignant and advanced oral tumors. HOXA5 and HOXC9 showed higher transcription factor-mediated interactions with neighboring HOX genes within and across the clusters. Additionally, HOXB9 and HOXC10 were predicted to directly regulate the G2-M checkpoint and hypoxia pathways. HOXA genes can be post-transcriptionally regulated through an antisense-mediated mechanism involving embedded HOX long noncoding RNAs (lncRNAs). Posterior HOX genes were more highly expressed than anterior HOX genes. The HOXC and HOXD cluster gene expression patterns were similar to those of the embedded lncRNAs. HOXA1, HOXC13 and HOXD10 were significantly correlated with the cancer hallmarks driving oral carcinogenesis.</p><p><strong>Conclusion: </strong>The functional consequence of HOX genes dysregulation was driven by diverse DNA and RNA epigenetic mechanisms affecting the transcriptional and post-transcriptional regulation contributing to the oral cancer progression.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"126"},"PeriodicalIF":4.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Martinostat as a novel HDAC inhibitor to overcome tyrosine kinase inhibitor resistance in chronic myeloid leukemia.","authors":"Haeun Yang, Vladimir Li, Su Jung Park, Sang Won Cheon, Anne Lorant, Aloran Mazumder, Jin Young Lee, Barbora Orlikova-Boyer, Claudia Cerella, Christo Christov, Gilbert Kirsch, Dag Erlend Olberg, Guy Bormans, Hyoung Jin Kang, Byung Woo Han, Michael Schnekenburger, Marc Diederich","doi":"10.1186/s13148-025-01921-0","DOIUrl":"10.1186/s13148-025-01921-0","url":null,"abstract":"<p><strong>Background: </strong>Chronic myeloid leukemia (CML) remains a therapeutic challenge, particularly in patients who develop resistance to standard tyrosine kinase inhibitors (TKIs) such as imatinib. Here, we present the first demonstration of the potent anti-leukemic activity of the histone deacetylase (HDAC) inhibitor martinostat in both TKI-sensitive and TKI-resistant CML.</p><p><strong>Methods and results: </strong>Structural and biochemical analyses confirmed the efficient and selective binding of martinostat to HDAC isoenzyme ligand-binding pockets, resulting in histone and tubulin hyperacetylation in both imatinib-sensitive and resistant CML cells, outperforming vorinostat, a clinically used HDAC inhibitor (HDACi). It selectively impaired CML cell proliferation and viability and induced apoptosis across various CML models, including resistant cell models and patient blasts, with minimal toxicity to healthy cells and low developmental toxicity in zebrafish. In addition to its single-agent efficacy, martinostat demonstrated enhanced anticancer effects when combined with imatinib, both in vitro and in vivo, significantly reducing tumor growth in resistant CML xenograft models. Mechanistically, mRNA-seq data showed that martinostat disrupted key survival signaling pathways and amplified apoptotic responses, contributing to its anticancer activity.</p><p><strong>Conclusions: </strong>These findings highlight the potential of martinostat as a selective, low-toxicity HDACi that, combined with TKIs, could provide an effective strategy to overcome drug resistance in CML and improve therapeutic outcomes.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"125"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RASGEF1C methylation for the distinguishment and classification of benign and malignant thyroid tumors.","authors":"Wenkang Yu, Yifei Yin, Mengxia Li, Haixia Huang, Junjie Li, Yi Zhang, Lun Zhu, Yifen Zhang, Xuandong Huang, Chenxia Jiang, Rongxi Yang","doi":"10.1186/s13148-025-01931-y","DOIUrl":"10.1186/s13148-025-01931-y","url":null,"abstract":"<p><strong>Background: </strong>The incidence of thyroid cancer (TC) has significantly increased, highlighting the need for effective and objective approaches for the early diagnosis of TC. This study aimed to explore RASGEF1C methylation as a biomarker for papillary thyroid cancer (PTC).</p><p><strong>Methods: </strong>Formalin-fixed paraffin-embedded samples from a total of 363 PTC and 409 benign thyroid nodules from multiple centers were analyzed. RASGEF1C methylation profiles were examined via MALDI-TOFF mass spectrometry. Statistical analysis was performed via logistic regression adjusted for covariates, nonparametric tests, and receiver operating characteristic (ROC) analysis. Additionally, 40 follicular thyroid cancer samples, 45 medullary thyroid cancer samples, and 7 anaplastic thyroid samples from three hospitals were afterward collected to compare methylation patterns across subtypes.</p><p><strong>Results: </strong>Hypomethylation of RASGEF1C in PTC was observed vs. BTN (all odds ratios (ORs) ≥ 1.57, p values < 0.001). Stratification analysis revealed a more pronounced association in younger patients, especially for BRAF V600E-positive PTC patients, than in individuals with benign tumors (all ORs ≥ 1.89, p values < 0.001). ROC analysis further demonstrated the outstanding diagnostic power of RASGEF1C hypomethylation for BRAF V600E-positive PTC cases (area under the curve (AUC) = 0.93), for cases < 55 years old (AUC = 0.88), and even for patients with a tumor length ≤ 1 cm (AUC = 0.83). Moreover, we observed the lowest RASGEF1C methylation level in anaplastic thyroid carcinoma, the most aggressive subtype of TC. Our results revealed similar RASGEF1C hypomethylation between chronic lymphocytic thyroiditis and papillary thyroid cancer, whereas RASGEF1C methylation in subacute thyroiditis patients was similar to that in the other benign subtypes.</p><p><strong>Conclusion: </strong>Our study revealed RASGEF1C methylation as a promising biomarker for distinguishing and classifying benign and malignant thyroid tumors and even provided epigenetic evidence for the inflammatory-cancer transformation. Nevertheless, the limitation of tissue-based biomarkers should be well noted, and the development of more accessible biomarkers warrants further exploration in the future.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"124"},"PeriodicalIF":4.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple highly methylated CpG sites as potential epigenetic markers for the diagnosis of prostate cancer.","authors":"Jean-Pierre Roperch, Guillaume Charbonnier, Sandy Figiel, Alastair Lamb, Ian Mills, Claude Hennion, Géraldine Cancel-Tassin, Olivier Cussenot","doi":"10.1186/s13148-025-01930-z","DOIUrl":"10.1186/s13148-025-01930-z","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) remains the leading cause of cancer deaths in men. The prostate-specific antigen (PSA) test is widely used for PCa screening, but it lacks specificity and can lead to over-diagnosis and over-treatment. New, effective and affordable markers are therefore needed.</p><p><strong>Results: </strong>Using enzymatic methyl sequencing (EM-Seq), methylation-specific PCR (MS-PCR), and transcriptomics including a spatial approach, we analyzed tumor and non-tumor samples from radical prostatectomy specimens. Comprehensive methylome was performed in 15 paired samples of prostate cancer and their adjacent non-tumor tissue by EM-Seq. From over 4-million differentially methylated CpG sites, we identified 66 CpGs sites representing eight genes: CLDN5, GSTP1, NBEAL2, PRICKLE2, SALL3, TAMALIN/GRASP, TJP2, and TMEM106A which were hypermethylated in PCa tissues (p-value < 0.0001), and were confirmed by MS-PCR. A very good correlation between EM-Seq and MS-PCR results was observed (Pearson's correlation of 0.93). Differential expression of these candidate genes was analyzed first, using an Affymetrix RNA array dataset from a cohort of 68 non-tumor samples and 101 tumors with different aggressiveness patterns and, second, by in situ expression using Visium 10X spatial genomics transcriptomics on eight prostate tissue sections with different tumor grades and non-tumor glands. Lower expression level was found, using RNA arrays, in tumor compared to non-tumor tissues for six of the eight genes (p ≤ 0.0001) and in tumor glands with high aggressiveness compared to non-tumor glands (p <  0.0001) for the eight genes using in situ transcriptomics.</p><p><strong>Conclusions: </strong>Our study identifies promising DNA methylation markers for the diagnosis of prostate cancer.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"122"},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin levels at 18-20 gestational weeks in pregnant women with obesity are associated with newborn abdominal fat deposition and DNA methylation in cord blood.","authors":"Alice Maguolo, Josefine Jönsson, Alexander Perfilyev, Allan Vaag, Emma Malchau Carlsen, Kirsten Nørgaard, Paul W Franks, Kristina M Renault, Charlotte Ling","doi":"10.1186/s13148-025-01923-y","DOIUrl":"10.1186/s13148-025-01923-y","url":null,"abstract":"<p><p>We assessed if fasting plasma insulin levels in pregnant women with obesity are associated with newborns' abdominal fat deposition (dual-energy X-ray absorptiometry) and with cord blood DNA methylation (450k array) in 232 mother-child pairs from the Treatment of Obese Pregnant women (TOP) study. Fasting maternal insulin at 18-20gw was associated with abdominal/total fat mass ratio in newborns independent of multiple potential confounders (β = 0.23[95%CI: 0.01; 0.45], P = 0.041) and with cord blood DNA methylation at CpG sites annotated to C11orf54 and RARB (FDR < 10%), both genes potentially involved in metabolic programming. In conclusion, maternal insulin levels in pregnancy were associated with adiposity traits and epigenetics in the offspring.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"123"},"PeriodicalIF":4.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical performance evaluation of a plasma dual-target methylation test for the detection of primary liver cancer: a multicenter study.","authors":"Zhigao Xu, Wanping Chen, Hongsheng Wei, Kui Tan, Lianglu Zhang, Lanlan Dong, Wenjin Liang, Xin Zhou, Tao Zhang, Jian Chen, Chuang Peng, Zhongxin Wang, Shaojun Ye, Qifa Ye","doi":"10.1186/s13148-025-01920-1","DOIUrl":"10.1186/s13148-025-01920-1","url":null,"abstract":"<p><strong>Background: </strong>Primary liver cancer (PLC) is a global health concern. The plasma dual-target methylation (PDTM) test, which interrogates the methylation status of GNB4 and Riplet, exhibits a commendable ability to discriminate hepatocellular carcinoma (HCC) from controls. Nevertheless, its performance in detecting PLC in larger populations remains to be validated.</p><p><strong>Results: </strong>A multicenter, double-blind, cross-sectional study was conducted. Blood samples were collected from all participants for the PDTM test, which is based on a triplex quantitative methylation-specific polymerase chain reaction (qMSP) platform. Additionally, Sanger sequencing was performed to confirm the accuracy of methylation detection by the PDTM test. The study enrolled 430 PLC patients and 752 controls. The PDTM test demonstrated an overall sensitivity of 92.3% (95% confidence interval [CI], 89.4-94.7) for PLC patients and an overall specificity of 93.4% (95% CI, 91.3-95.0) for controls with benign liver disease (BLD) or non-liver primary malignancies (NLPM). Specifically, the sensitivities of the PDTM test for patients with HCC, intrahepatic cholangiocarcinoma (ICC) or early-stage (TNM stages I and II) PLC were 91.9% (95% CI, 87.6-95.0), 93.3% (95% CI, 85.9-97.5) and 88.7% (95% CI, 83.9-92.5), respectively. Furthermore, the kappa values for both GNB4 and Riplet between the PDTM test and Sanger sequencing exceeded 0.99, indicating a high level of consistency.</p><p><strong>Conclusions: </strong>The PDTM test demonstrates excellent diagnostic performance for PLC, particularly in cases of early-stage PLC. It is a promising early screening or surveillance tool for PLC, and further prospective research is required to ascertain its full utility.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"121"},"PeriodicalIF":4.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol consumption and DNA methylation: an epigenome-wide association study within the French E3N cohort.","authors":"Dzevka Dragic, Fanny Artaud, Mojgan Karimi, Thérèse Truong, Laura Baglietto, Jean-François Deleuze, Caroline Diorio, Gianluca Severi","doi":"10.1186/s13148-025-01893-1","DOIUrl":"10.1186/s13148-025-01893-1","url":null,"abstract":"<p><strong>Background: </strong>Alcohol consumption can have harmful effects on health, depending on the quantity and frequency. Understanding the underlying molecular mechanisms is essential to grasp its health consequences. The study aimed to assess the association between alcohol consumption and blood DNA methylation, an epigenetic mechanism that controls gene expression.</p><p><strong>Methods: </strong>The epigenome-wide association study (EWAS) included 1,538 women from a case-cohort study within the French E3N cohort. Weighted linear mixed-effects models were used to assess the associations between self-reported alcohol consumption (in g/day in 1993) and DNA methylation at 715,986 CpGs measured with the HumanMethylationEPIC Beadchip. Women were cancer-free at blood collection in 1995-1999.</p><p><strong>Results: </strong>Of the 715,986 sites analyzed, 19,255 were associated with alcohol consumption (FDR < 0.05). Over-representation analysis highlighted enrichment of genes involved in cancer, the nervous system and aging. Of these 19,255 sites, 1,528 were replicated in an independent case-control study, with 85 also identified in other EWAS. Notably, at least six studies reported sites in SLC7A11, ANP32B, MCM2, HNRNPA1, SNORD30, and TRA2B genes.</p><p><strong>Conclusions: </strong>Several potential methylation markers for alcohol consumption, documented prior to blood sampling, have been identified. The link between these sites and chronic diseases should be investigated to understand the molecular mechanisms underlying the harmful effects of alcohol consumption on health.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"118"},"PeriodicalIF":4.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}