Clinical Epigenetics最新文献

{"title":"Work-related stress and burnout: Is epigenetic aging the missing link?","authors":"Julian Eder, Friederike Sophie David, Sabrina Illius, Nicole Rothe, Magdalena Katharina Wekenborg, Andreas Walther, Marlene Penz, Juulia Jylhävä, Robert Miller, Clemens Kirschbaum, Nina Alexander","doi":"10.1186/s13148-025-01968-z","DOIUrl":"10.1186/s13148-025-01968-z","url":null,"abstract":"<p><strong>Background: </strong>Work-related stress is a well-established contributor to mental health decline, particularly in the context of burnout, a state of prolonged exhaustion. Epigenetic clocks, which estimate biological age based on DNA methylation (DNAm) patterns, have been proposed as potential biomarkers of chronic stress and its impact on biological aging and health. However, their role in mediating the relationship between work-related stress, physiological stress markers, and burnout remains unclear.</p><p><strong>Methods: </strong>Here, we analyzed DNAm data from 296 employed individuals (n_female = 202; M_age = 45.4; SD_age = 11.3; range_age = 19.5-67.1) from the longitudinally assessed cohort of the Dresden Burnout Study to investigate whether epigenetic aging mediates the relationship between work-related stress (effort-reward imbalance), hair glucocorticoids (cortisol, cortisone), and burnout symptoms. We examined four epigenetic clocks (DNAm Skin&Blood Age, DNAm PhenoAge, DNAm GrimAge, and DNAm GrimAge2) at baseline and follow-up (one year later). Additional mediation analyses were conducted for depressive symptoms to distinguish their potential effects from those specifically associated with burnout symptoms.</p><p><strong>Results: </strong>As expected, work-related stress at baseline significantly predicted burnout (β = .47, p < .001) and depressive symptoms (β = .32, p < .001) at follow-up. However, epigenetic aging did not mediate these relationships, neither cross-sectionally (indirect effects of epigenetic age acceleration [EAA]: ß_burnout = [-.0008, -.00001]) nor longitudinally (indirect effects of changes in raw clock estimates: ß_burnout = [-.002, .007]). Furthermore, work-related stress and hair glucocorticoids were not significantly associated with any epigenetic age markers (all p values > .117), and both EAA and changes in epigenetic aging over time were unrelated to burnout or depressive symptoms (all p values > .190). Sensitivity analyses adjusting for blood cell composition and technical variance confirmed these findings.</p><p><strong>Conclusions: </strong>Consequently, our results do not support the hypothesis that epigenetic aging serves as a biological mechanism linking work-related stress or biological stress markers to burnout symptoms. While work-related stress significantly predicts burnout and depressive symptoms, its association does not appear to be driven by epigenetic aging pathways in a low to moderately burdened population. These findings underscore the need for longer follow-up studies to explore alternative biological and psychosocial pathways that shape the long-term consequences of work-related stress on mental health.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"148"},"PeriodicalIF":4.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029019","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":"Epigenetic age acceleration in Turner and Klinefelter syndrome: Correlations with clinical aging markers.","authors":"Emma B Hasselholm, Jesper Just, Simon Chang, Anne Skakkebæk, Claus Højbjerg Gravholt","doi":"10.1186/s13148-025-01963-4","DOIUrl":"10.1186/s13148-025-01963-4","url":null,"abstract":"<p><strong>Background: </strong>The sex chromosome aneuploidies Turner syndrome (45,X; TS) and Klinefelter syndrome (47,XXY; KS) are associated with aging-related comorbidities, reduced life expectancy and genome-wide DNA methylation changes. This indicates that biological aging, reflecting physiological function rather than chronological age, is increased in both syndromes. To investigate whether DNA methylation patterns linked to physiological decline could contribute to the comorbidity patterns and reduced lifespan in TS and KS, we applied so-called epigenetic clocks to DNA methylation data from cohorts of TS (n = 57) compared to female controls (n = 33) and KS (n = 65) compared to male controls (n = 63). Additionally, we evaluated correlations between epigenetic age and clinical variables, aiming to identify clinical aging markers in TS and KS.</p><p><strong>Results: </strong>Comparing TS to female controls, all epigenetic clocks indicated advanced biological aging. Comparing KS to male controls, less evidence was observed although some epigenetic clocks indicated accelerated biological aging. Considering estrogen replacement therapy in TS, some epigenetic clocks found that treatment reduced biological age in TS. Correlating epigenetic clocks to clinical variables, several unfavorable outcomes-mainly related to body composition-correlated with age in controls. In TS, and in some cases KS, these correlations were diminished. In TS and KS, we instead found correlations between body composition and the rate of aging.</p><p><strong>Conclusion: </strong>We demonstrated that biological aging was clearly increased in sex chromosome aneuploidies, especially TS, potentially contributing to the severely reduced lifespan. Additionally, unfavorable changes in body composition, common in both TS and KS, and in particular in the presence of hypogonadism, could result in accelerated aging-or be the result thereof.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"147"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945369","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":"Selective disruption of DNMT1/ELK1 interactions induces DGKI re-expression and promotes temozolomide sensitivity of MGMT^methylated/DGKI^methylated glioblastoma.","authors":"Jean-Maxime Besson, Amandine Etcheverry, Arulraj Nadaradjane, Gwenola Bougras-Cartron, Marc Aubry, Jean-Sebastien Frenel, Alain Chevanieu, Marie Lopez, Jean Mosser, Pierre-François Cartron","doi":"10.1186/s13148-025-01943-8","DOIUrl":"10.1186/s13148-025-01943-8","url":null,"abstract":"<p><strong>Background: </strong>DNA methyltransferase (DNMT) inhibitors are emerging as a promising class of agents for personalized and targeted cancer therapy, particularly in malignancies with limited therapeutic options such as glioblastoma (GB). In GB, the MGMT/DGKI methylation profile serves as a biomarker for stratifying patients by treatment response. Specifically, the MGMT^methylated/DGKI^unmethylated profile is associated with favorable outcomes, whereas the MGMT^methylated/DGKI^methylated profile correlates with poor outcome. These findings suggest that selective demethylation of DGKI without altering MGMT or inducing widespread genomic hypomethylation, which may promote tumorigenesis, could represent a novel and more effective therapeutic strategy.</p><p><strong>Results: </strong>Current DNMT inhibitors lack specificity for glioblastoma relevant methylation profiles, thereby limiting their therapeutic efficacy. To address this challenge, AlphaFold-based protein-protein interaction predictions were integrated with sequential chromatin immunoprecipitation assays and established DNMT1 interactome data. This integrative approach led to the identification of a DNMT1/ELK1 complex as a critical regulator of DGKI methylation. A peptide mimicking the DNMT1/ELK1 interface, designated EXD^DNMT1/ELK1, was designed and shown to induce selective DGKI demethylation without altering MGMT or inducing global DNA hypomethylation. Notably, EXD^DNMT1/ELK1 did note promote cellular proliferation or invasion, and successfully restored sensitivity to standard glioblastoma therapy in both cellular and in vivo models. These findings also support the use of MGMT and DGKI methylation levels in cell-free DNA as potential biomarkers to identify patients likely to benefit from EXD^DNMT1/ELK1 treatment.</p><p><strong>Conclusion: </strong>This study identifies a clinically actionable biomarker (MGMT^Methylated/DGKI^Methylated), detectable in both solid and liquid biopsies, enabling patient stratification. Furthermore, it establishes EXD^DNMT1/ELK1 as a highly selective epigenetic therapeutic agent to treat GB patients.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"146"},"PeriodicalIF":4.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945375","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":"Regulation of cisplatin resistance in lung cancer by epigenetic mechanisms.","authors":"Xiaoyan Yu, Luyu Jia, Qing Tang, Qichun Zhou, Genshu Wang, Sumei Wang","doi":"10.1186/s13148-025-01961-6","DOIUrl":"https://doi.org/10.1186/s13148-025-01961-6","url":null,"abstract":"<p><p>Lung cancer remains one of the most prevalent and lethal malignancies worldwide, responsible for nearly 1.8 million deaths annually, which accounts for approximately 18.7% of global cancer-related mortality. Cisplatin, a highly effective and widely utilized anticancer drug, is particularly effective against solid tumors and serves as a cornerstone of adjuvant chemotherapy for lung cancer. Despite continuous optimization of cisplatin-based chemotherapy regimens, the emergence of cisplatin resistance frequently results in treatment failure, significantly limiting its clinical utility and therapeutic efficacy. To address this challenge, researchers have extensively investigated the biological mechanisms underlying cisplatin resistance, including impaired DNA repair pathways and inhibition of apoptosis. Among these mechanisms, epigenetic regulation-encompassing DNA methylation, histone modifications, and noncoding RNA (ncRNA) regulation-has emerged as a critical factor in mediating cisplatin resistance by modulating gene expression and signaling pathways. This review comprehensively explores the role of epigenetic mechanisms in cisplatin resistance in lung cancer, highlighting recent research findings and their potential implications for developing strategies to overcome drug resistance.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"145"},"PeriodicalIF":4.4,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945349","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":"Landscape analysis of m5C modification regulators unveils DNMT1-mediated dysregulated pyrimidine metabolism in hepatocellular carcinoma.","authors":"Xuhui Zhao, Shengwei Mao, Yuan Fang, Jiafeng Chen, Lifu Bi, Jie Li, Jinglei Wu, Jun Gao, Shiguang Yang, Jialu Fu, Xiaoling Wu, Guiqi Zhu, Zheng Tang, Yinghong Shi, Jian Zhou, Jia Fan, Xingxing Zhang, Jinling Jiang, Weiren Liu","doi":"10.1186/s13148-025-01956-3","DOIUrl":"https://doi.org/10.1186/s13148-025-01956-3","url":null,"abstract":"<p><p>The 5-methylcytosine (m5C) post-transcriptional modification has been linked with the development and progression of a variety of cancers. However, its specific functions and their underlying mechanisms are poorly understood in hepatocellular carcinoma (HCC). The present study showed abnormally increased levels of m5C modifications in HCC that were positively correlated with both HCC progression and worse patient prognosis. Landscape profiling of metabolic characteristics showed dysregulation of pyrimidine metabolism mediated by DNA methyltransferases 1 (DNMT1), and cyclin-dependent kinase 1 (CDK1) was identified as a downstream effector upregulated by DNMT1 in an m5C-dependent manner, with CDK1 promoting pyrimidine metabolism. Knockdown of DNMT1 or CDK1 was found to reduce the proliferation, invasion, and migration of HCC cells in vitro. Moreover, pharmacological targeting of the DNMT1/CDK1/pyrimidine metabolism axis with specific inhibitors effectively suppressed tumor progression in HCC model mice. These findings demonstrated the landscape profiles of m5C-related metabolic features in HCC, showing stabilization of CDK1 mRNA by DNMT1-mediated m5C modification, resulting in the promotion of pyrimidine metabolism, a crucial feature of HCC progression. These insights highlight the therapeutic potential of targeting the DNMT1/CDK1/pyrimidine metabolism axis as a strategy for combating HCC.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"144"},"PeriodicalIF":4.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945294","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 of food sensitization in a French-Canadian population.","authors":"Bénédicte L Tremblay, Anne-Marie Madore, Catherine Laprise","doi":"10.1186/s13148-025-01951-8","DOIUrl":"10.1186/s13148-025-01951-8","url":null,"abstract":"<p><strong>Background: </strong>Food allergy (FA) is a great public health concern with an increased prevalence in the last decades. The underlying development mechanisms of FA and food sensitization (FS), which represents the first stage of development of FA, are influenced by environmental, epigenetic, and genetic factors. DNA methylation is an important epigenetic mediator of gene-environment interactions and key to understanding these mechanisms. Studies have linked whole-genome DNA methylation profile to FA and FS, but they all use methylation arrays. Methylation sequencing captures target regions of methylome with an extensive coverage. Thus, our objective was to identify CpG sites in genome-wide immune regulatory regions associated with FS and test their association with genetic variants using methylation quantitative trait loci (mQTL) analysis in French-Canadian individuals.</p><p><strong>Results: </strong>In 114 individuals from the Saguenay-Lac-Saint-Jean asthma family cohort, a total of 10 CpG sites out of 5,233,004 CpG sites were associated with the FS status (P < 1 × 10^-8). CpG sites were located in 10 genes (ARRDC1, B9D1, CFL1, CROCC, DHX36, DND1, PMS1, RASSF1, TOP2A, and USP21) all of which were associated with immune response and allergic diseases (allergy, asthma, atopic dermatitis, and allergic rhinitis) in the literature. Almost all individuals with FS clustered based on the methylation levels of these CpG sites which reinforces their importance and relevance to discriminate individuals with and without FS in our cohort. Among the top 10 most significant CpG sites, five were associated with 478 genetic variants in trans-mQTL (FDR < 1 × 10^-8).</p><p><strong>Conclusions: </strong>To our knowledge, this is a unique association study between FS and DNA methylation using targeted bisulfite sequencing across the genome. This approach provides high-resolution assessment of genome-wide functional methylome that yields valuable understandings to this field of research. The results reveal potential relationships between FS, CpG sites, and genetic variants located in genes involved in allergic diseases. This provides potential insights on the underlying effects of DNA methylation and genetic variants on FS and possibly the pathogenesis of FA. Further epigenome-wide studies on larger samples combined with genome-wide genotyping are needed to validate the results and verify the biological potential of these CpG sites.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"143"},"PeriodicalIF":4.4,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871776","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":"Deciphering the methylation landscape of long noncoding RNAs in hepatocellular carcinoma: a focus on LINC00942.","authors":"Zhaoqi Shi, Xiaolong Liu, Duguang Li, Jing Yang, Haonan Chen, Hui Lin, Xiaoxiao Fan","doi":"10.1186/s13148-025-01952-7","DOIUrl":"10.1186/s13148-025-01952-7","url":null,"abstract":"<p><strong>Background: </strong>Conduct a comprehensive genome-wide methylomic analysis of long noncoding RNA (lncRNA) genes in hepatocellular carcinoma (HCC) and identify specific lncRNAs for subsequent functional validation.</p><p><strong>Methods: </strong>We conducted a methylation microarray analysis on 11 HCC samples alongside adjacent non-tumor tissue specimens. This analysis was integrated with The Cancer Genome Atlas data and the Gene Expression Omnibus for a comprehensive methylomic evaluation. Following this, a LASSO retrospective analysis was employed to develop a prognostic model for HCC, utilizing the methylation levels of specific lncRNA genes. Ultimately, LINC00942 was identified as a significant candidate within the model, and its biological effects in HCC cells were investigated through both in vitro and in vivo experiments. Additionally, potential downstream target genes of LINC00942 were elucidated using western blot analysis.</p><p><strong>Results: </strong>Genome-wide hypomethylation and CpG island hypermethylation within lncRNA genes were observed in HCC. Furthermore, a prognostic model utilizing the methylation levels of five specific lncRNA genes has demonstrated high accuracy in predicting the prognosis of patients diagnosed with HCC. LINC00942, an identified lncRNA within the model, exhibits hypomethylation and elevated expression levels in HCC. Methylation within the promoter region has been shown to suppress its expression in HCC cells. Both in vivo and in vitro studies have demonstrated that the silencing of LINC00942 leads to a decrease in the proliferation, migration, and invasion of HCC cells. Flow cytometry analyses revealed a significant increase in cell cycle arrest and apoptosis in HCC cells following the knockdown of LINC00942. The result of western blot indicates that cyclin D1, CDK2, and BAX are probable downstream target molecules of LINC00942.</p><p><strong>Conclusions: </strong>A substantial quantity of lncRNAs is transcriptionally modulated by methylation in HCC. The demethylation of LINC00942 within its promoter region facilitates the upregulation of LINC00942 expression, thereby contributing to its function as an oncogene in HCC.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"142"},"PeriodicalIF":4.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859008","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":"Detection of genome-wide methylation changes in bladder cancer by long-read sequencing of urinary DNA.","authors":"Anshita Goel, Benjamin J Tura, Joanne D Stockton, Nicholas Tovey, Luke Ames, Andrew D Beggs, Maurice P Zeegers, Nicholas D James, K K Cheng, Richard T Bryan, Douglas G Ward, Roland Arnold","doi":"10.1186/s13148-025-01946-5","DOIUrl":"10.1186/s13148-025-01946-5","url":null,"abstract":"<p><strong>Background: </strong>Non-invasive urine tests for bladder cancer (BC) could reduce dependence on flexible cystoscopy for diagnosis and surveillance. Most recent developments in urine testing are based on targeted detection of genomic and/or epigenomic markers. We hypothesised that long-read whole-genome sequencing of urinary DNA with direct methylation profiling may allow accurate BC detection and insights into disease biology. However, the feasibility of such an approach has not yet been reported.</p><p><strong>Methods: </strong>We applied long-read whole-genome sequencing with direct methylation detection to urine cell pellet DNA (ucpDNA) from 21 haematuria clinic patients: 13 BCs and 8 non-BCs. The modkit Hidden Markov Model algorithm was used to define differentially methylated regions across the genome. The ability to discriminate between BC and non-BC, and the cellular pathways affected were tested using PCA, h-clust and GSEA.</p><p><strong>Results: </strong>We observed global hypomethylation and cancer-specific patterns of promoter hypermethylation in urine from BC patients. Sequencing of a single ucpDNA sample per flow cell yielded read depths of 18-34x; furthermore, BC methylation patterns were also evident with 2-5x multiplex sequencing. Copy number changes were also evident in ucpDNAs from BC patients. A limitation of the study is the small number of samples analysed; however, the detection of cancer-specific events demonstrates the feasibility of the approach, both in single and multiplexed flow-cell runs.</p><p><strong>Conclusions: </strong>Even at low-read depths, genome-wide methylation patterns in urinary DNA reflect the presence of BC, potentially permitting rapid, non-invasive and cost-effective BC detection.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"141"},"PeriodicalIF":4.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820700","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":"BRCA1 promoter methylation predicts PARPi response in ovarian cancer: insights from the KOMET study.","authors":"Léna Nougarede, Florence Hazane-Puch, Florence de Fraipont, Emmanuelle Jacquet, Marie Bidart","doi":"10.1186/s13148-025-01917-w","DOIUrl":"10.1186/s13148-025-01917-w","url":null,"abstract":"<p><strong>Objectives: </strong>PARP inhibitors (PARPi) have become the new standard maintenance treatment for patients with advanced homologous recombination deficiency (HRD) ovarian cancer; they are also used upon platinum-sensitive relapse. HRD in ovarian cancer is primarily assessed through BRCA genes mutations and genomic scar scores, which are key biomarkers forecasting PARPi benefit. However, the role of BRCA1 promoter methylation in guiding clinical management is unclear. Evidence is needed to improve patient selection before initiating PARPi and to minimize PARPi-related toxicities. Our study aimed to determine the clinical relevance of BRCA1 promoter methylation for patients with ovarian carcinoma.</p><p><strong>Method: </strong>The KOMET (Ovarian Cancer Methylation) study is a single-center retrospective study involving 88 ovarian cancer patients treated between January 2021 and July 2024. Methylation was assessed using Methylation specific high-resolution melting (MS-HRM). Outcomes were measured based on progression-free survival (PFS) from diagnosis and from the initiation of PARPi treatment, as well as overall survival (OS).</p><p><strong>Results: </strong>A methylated BRCA1 promoter was detected in 17 out of 88 (19%) tumor tissues. Statistically, PFS from PARPi initiation was significantly different between the BRCA1 methylated promoter (BRCA1mp) group and the BRCA1 unmethylated promoter and HRD negative (BRCA1up HRD-) group (p value = 0.0003 log rank test; Hazard Ratio (HR), 95% CI 0.04-0.40). OS was also significantly different between these groups (p value = 0.047 log rank test; HR = 0.30, 95% CI 0.10-0.84), as was PFS from diagnosis (p value = 0.02 log rank test; HR = 0.43, 95% CI 0.21-0.89).</p><p><strong>Conclusion: </strong>BRCA1 promoter methylation in ovarian cancer is associated with a better response to PARPi and platinum salt chemotherapy than tumors without promoter methylation or classical homologous recombination deficiency. Patients with unmethylated BRCA1 promoters and HRD-negative tumors appeared to have a poorer prognosis in terms of PFS from diagnosis. BRCA1 methylation should be considered as a theragnostic biomarker for initiation of PARPi.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"140"},"PeriodicalIF":4.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798361","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":"Lactylation modifications in urological diseases: molecular mechanisms and biological implications.","authors":"Songyuan Yang, Zehua Ye, Sheng Zhao, Fan Cheng","doi":"10.1186/s13148-025-01947-4","DOIUrl":"10.1186/s13148-025-01947-4","url":null,"abstract":"<p><p>Urological disorders encompass a broad spectrum of medical conditions that affect the kidneys, ureters, bladder, and urethra. Among these, urinary tract infections, kidney stones, renal dysfunction, and urological malignancies are commonly observed, each exhibiting distinct pathophysiological mechanisms. Due to their diverse etiologies and heterogeneous nature, strategies for prevention and treatment must be tailored to the specific characteristics of each disease. Lactylation, a recently recognized post-translational modification, arises from excessive lactate accumulation. This biochemical alteration occurs in histones, where it influences gene transcription, and in non-histone proteins, where it modulates their functional properties. Recent research indicates that lactylation significantly contributes to the development of various urological diseases by affecting key biological processes such as inflammation, angiogenesis, lipid metabolism, and fibrosis. Given its involvement in these pathological pathways, precise regulation of lactylation presents a promising avenue for both prognostic evaluation and therapeutic intervention in urological disorders. This review offers a thorough examination of lactylation, exploring its biological functions and mechanistic roles in urological diseases. In particular, it underscores the impact of lactylation on disease initiation and progression while providing novel insights into its therapeutic and preventive potential. By clarifying the role of lactylation in urological pathology, this analysis aims to support future scientific inquiries and clinical advancements in this expanding field.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"139"},"PeriodicalIF":4.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12330050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793626","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}