Azar Tahghighi, Effat Seyedhashemi, Javad Mohammadi, Arash Moradi, Aria Esmaeili, Majid Pornour, Kimia Jafarifar, Shahla Mohammad Ganji
{"title":"Epigenetic marvels: exploring the landscape of colorectal cancer treatment through cutting-edge epigenetic-based drug strategies.","authors":"Azar Tahghighi, Effat Seyedhashemi, Javad Mohammadi, Arash Moradi, Aria Esmaeili, Majid Pornour, Kimia Jafarifar, Shahla Mohammad Ganji","doi":"10.1186/s13148-025-01844-w","DOIUrl":"10.1186/s13148-025-01844-w","url":null,"abstract":"<p><p>Epigenetics is currently considered the investigation of inheritable changes in gene expression that do not rely on DNA sequence alteration. Significant epigenetic procedures are involved, such as DNA methylations, histone modifications, and non-coding RNA actions. It is confirmed through several investigations that epigenetic changes are associated with the formation, development, and metastasis of various cancers, such as colorectal cancer (CRC). The difference between epigenetic changes and genetic mutations is that the former could be reversed or prevented; therefore, cancer treatment and prevention could be achieved by restoring abnormal epigenetic events within the neoplastic cells. These treatments, consequently, cause the anti-tumour effects augmentation, drug resistance reduction, and host immune response stimulation. In this article, we begin our survey by exploring basic epigenetic mechanisms to understand epigenetic tools and strategies for treating colorectal cancer in monotherapy and combination with chemotherapy or immunotherapy.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"34"},"PeriodicalIF":4.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476313","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}
Saher Daredia, Dennis Khodasevich, Nicole Gladish, Hanyang Shen, Jamaji C Nwanaji-Enwerem, Anne K Bozack, Belinda L Needham, David H Rehkopf, Julianna Deardorff, Andres Cardenas
{"title":"Timing of menarche and menopause and epigenetic aging among U.S. adults: results from the National Health and Nutrition Examination Survey 1999-2002.","authors":"Saher Daredia, Dennis Khodasevich, Nicole Gladish, Hanyang Shen, Jamaji C Nwanaji-Enwerem, Anne K Bozack, Belinda L Needham, David H Rehkopf, Julianna Deardorff, Andres Cardenas","doi":"10.1186/s13148-025-01827-x","DOIUrl":"10.1186/s13148-025-01827-x","url":null,"abstract":"<p><p>Reproductive aging, including timing of menarche and menopause, influences long-term morbidity and mortality in women, yet underlying biological mechanisms remain poorly understood. Using DNA methylation-based biomarkers, we assessed associations of age at menarche (N = 1,033) and menopause (N = 658) with epigenetic aging in a nationally representative sample of women ≥ 50 years. Later age at menopause was associated with lower GrimAge epigenetic age deviation ( <math><mi>B</mi></math> = - 0.10 years, 95% CI: - 0.19, - 0.02). No associations were observed for menarche timing. This suggests a connection between earlier menopause and biological aging, with potential clinical implications for identifying those at high risk for age-related disease.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"31"},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472406","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}
Bastien Ducreux, Catherine Patrat, Julie Firmin, Lucile Ferreux, Charles Chapron, Louis Marcellin, Guillaume Parpex, Mathilde Bourdon, Daniel Vaiman, Pietro Santulli, Patricia Fauque
{"title":"Systematic review on the DNA methylation role in endometriosis: current evidence and perspectives.","authors":"Bastien Ducreux, Catherine Patrat, Julie Firmin, Lucile Ferreux, Charles Chapron, Louis Marcellin, Guillaume Parpex, Mathilde Bourdon, Daniel Vaiman, Pietro Santulli, Patricia Fauque","doi":"10.1186/s13148-025-01828-w","DOIUrl":"10.1186/s13148-025-01828-w","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis appears to have a multilayered etiology, with genetic and epigenetic factors each contributing half of the pathogenesis. The molecular processes that underlie the onset of endometriosis are yet unclear, but it is assumed that an important contributor in the etiopathology of the disease is DNA methylation.</p><p><strong>Methods: </strong>We conducted a systematic review of the literature regarding DNA methylation in endometriosis following PRISMA guidelines. Records were obtained from PubMed and Web of Science on May 31, 2024. Original research articles analyzing regional or genome-wide DNA methylation in patients with confirmed endometriosis (by surgery and/or histological examination) were given consideration for inclusion. Only human studies were included, and there were no restrictions on the types of tissue that was analyzed (i.e., endometrium, blood, or fetal tissue). The study selection process was run by two manual reviewers. In parallel, an adapted virtual artificial intelligence-powered reviewer operated study selection and results were compared with the manual reviewers' selection. Studies were divided into targeted (e.g., single gene or region level) and epigenome-wide association studies. For each, we extracted a list of genes studied with precise location of CpGs analyzed and the DNA methylation status according to the groups compared. Quality assessment of studies was performed following the Newcastle-Ottawa scale. Quality of evidence was graded following the Grading of Recommendations Assessment, Development and Evaluation.</p><p><strong>Results: </strong>A total of 955 studies were screened, and 70 were identified as relevant for systematic review. Our analyses displayed that endometriosis could be polyepigenetic and with alterations in specific genes implicated in major signaling pathways contributing to the disease etiopathology (cell proliferation, differentiation, and division [PI3K-Akt and Wnt-signaling pathway], cell division [MAPK pathway], cell adhesion, cell communication, developmental processes, response to hormone, apoptosis, immunity, neurogenesis, and cancer).</p><p><strong>Conclusion: </strong>Our systematic review indicates that endometriosis is associated with DNA methylation modifications at specific genes involved in key endometrial biological processes, particularly in the ectopic endometrium. As DNA methylation appears to be an integral component of the pathogenesis of endometriosis, the identification of DNA methylation biomarkers would likely help better understand its causes and aggravating factors as well as potentially facilitate its diagnosis and support the development of new therapeutic approaches.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"32"},"PeriodicalIF":4.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476316","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":"Glucocorticoid exposure-induced alterations in epigenetic age from human preterm infants and human lung fibroblasts and hippocampal neuronal cells.","authors":"Xiaohui Wu, Chenglin Lu, Zhiying Deng, Wenbo Xiao, Hongyu Ni, Cunyou Zhao","doi":"10.1186/s13148-025-01837-9","DOIUrl":"10.1186/s13148-025-01837-9","url":null,"abstract":"<p><strong>Background: </strong>Maternal antenatal corticosteroid treatment is standard care to accelerate fetal maturation. However, there are growing concerns that antenatal corticosteroid administration may harm fetal neurodevelopment. Quantitative assessments of the effects of antenatal corticosteroid on the neonates have not been performed and poorly understood about their complex biology.</p><p><strong>Results: </strong>We collected Methylation BeadChips-generated DNA methylation data from the Gene Expression Omnibus (GEO) database and then employed \"multi-tissue predictor\" to quantify the DNAm age of saliva from 36 preterm neonates, which were stratified by the absence (n = 12) or presence (n = 24) of antenatal corticosteroid exposure, as well as 36 full-term neonates. Next, the DNAm age of human lung fibroblast IMR90 cells and human fetal multipotent hippocampal progenitor HPC cells, with or without glucocorticoid treatment, was also determined. We observed that the DNAm age of full-term neonates was significantly higher than that of the preterm neonates, and antenatal corticosteroid exposure accelerated the DNAm age of preterm neonates, while glucocorticoid exposure accelerated the DNAm age of IMR90 cells. Conversely, dexamethasone exposure delayed the DNAm age of HPC cells during the proliferation phase. It is noteworthy that 65% of the differentially methylated probes (DMPs) linked to the multi-tissue predictor marked CpGs and corticosteroid exposure in IMR90 cells exhibited comparable methylation patterns with the DMPs associated with the antenatal corticosteroid exposure in preterm neonates. Conversely, the majority of these DMPs exhibited inverse methylation alterations in dexamethasone-induced HPC cells. Furthermore, the epigenome-wide association study (EWAS) trait enrichment analyses of the DMPs linked to the antenatal corticosteroid exposure in preterm neonates revealed significant associations with prenatal adverse environmental exposure, growth and development, and neuropsychiatric disorders.</p><p><strong>Conclusions: </strong>Our results identified the cellular and molecular evidences of epigenetic clock changes in neonatal growth and developmental trajectories with the interference of antenatal corticosteroid treatment and provided potential clinical guidance for the future development of noninvasive fetal assessments to identify pregnant women who could benefit from antenatal corticosteroid in a wider gestational age.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"29"},"PeriodicalIF":4.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467233","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}
Zhonghua Wang, Ziwen Liu, Mengxin Lv, Zhou Luan, Tao Li, Jinhua Hu
{"title":"Novel histone modifications and liver cancer: emerging frontiers in epigenetic regulation.","authors":"Zhonghua Wang, Ziwen Liu, Mengxin Lv, Zhou Luan, Tao Li, Jinhua Hu","doi":"10.1186/s13148-025-01838-8","DOIUrl":"10.1186/s13148-025-01838-8","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and its onset and progression are closely associated with epigenetic modifications, particularly post-translational modifications of histones (HPTMs). In recent years, advances in mass spectrometry (MS) have revealed a series of novel HPTMs, including succinylation (Ksuc), citrullination (Kcit), butyrylation (Kbhb), lactylation (Kla), crotonylation (Kcr), and 2-hydroxyisobutyrylation (Khib). These modifications not only expand the histone code but also play significant roles in key carcinogenic processes such as tumor proliferation, metastasis, and metabolic reprogramming in HCC. This review provides the first comprehensive analysis of the impact of novel HPTMs on gene expression, cellular metabolism, immune evasion, and the tumor microenvironment. It specifically focuses on their roles in promoting tumor stem cell characteristics, epithelial-mesenchymal transition (EMT), and therapeutic resistance. Additionally, the review highlights the dynamic regulation of these modifications by specific enzymes, including \"writers,\" \"readers,\" and \"erasers.\"</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"30"},"PeriodicalIF":4.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467241","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}
Oleksii Nikolaienko, Garnet L Anderson, Rowan T Chlebowski, Su Yon Jung, Holly R Harris, Stian Knappskog, Per E Lønning
{"title":"MGMT epimutations and risk of incident cancer of the colon, glioblastoma multiforme, and diffuse large B cell lymphomas.","authors":"Oleksii Nikolaienko, Garnet L Anderson, Rowan T Chlebowski, Su Yon Jung, Holly R Harris, Stian Knappskog, Per E Lønning","doi":"10.1186/s13148-025-01835-x","DOIUrl":"10.1186/s13148-025-01835-x","url":null,"abstract":"<p><strong>Background: </strong>Constitutional BRCA1 epimutations (promoter hypermethylation) are associated with an elevated risk of triple-negative breast cancer and high-grade serous ovarian cancer. While MGMT epimutations are frequent in colon cancer, glioblastoma, and B-cell lymphoma, it remains unknown whether constitutional MGMT epimutations are associated with risk of any of these malignancies.</p><p><strong>Methods: </strong>We designed a nested case-control study, assessing potential associations between MGMT epimutations in blood from healthy individuals and subsequent risk of incident cancer. The study cohort was drawn from postmenopausal women, participating in the Women's Health Initiative (WHI) study, who had not been diagnosed with either colon cancer, glioblastoma, or B-cell lymphoma prior to study entry. The protocol included n = 400 women developing incident left-sided and n = 400 women developing right-sided colon cancer, n = 400 women developing diffuse large B-cell lymphomas, all matched on a 1:2 basis with cancer-free controls, and n = 195 women developing incident glioblastoma multiforme, matched on a 1:4 basis. All cancers were confirmed in centralized medical record review. Blood samples, collected at entry, were analyzed for MGMT epimutations by massive parallel sequencing. Associations between MGMT methylation and incident cancers were analyzed by Cox proportional hazards regression.</p><p><strong>Results: </strong>Analyzing epimutations affecting the key regulatory area of the MGMT promoter, the hazard ratio (HR) was 1.07 (95% CI 0.79-1.45) and 0.80 (0.59-1.08) for right- and left-sided colon cancer, respectively, 1.13 (0.78-1.64) for glioblastoma, and 1.11 (0.83-1.48) for diffuse large B-cell lymphomas. Sensitivity analyses limited to subregions of the MGMT promoter and to individuals with different genotypes of a functional SNP in the MGMT promoter (rs16906252), revealed no significant effect on HR for any of the cancer forms. Neither did we observe any effect of rs16906252 status on HR for any of the cancer forms among individuals methylated or non-methylated at the MGMT promoter.</p><p><strong>Conclusions: </strong>Constitutional MGMT promoter methylation in normal tissue is not associated with an increased risk of developing colon cancer, glioblastoma, or B-cell lymphoma.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"28"},"PeriodicalIF":4.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467237","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":"Diagnostic utility of single-locus DNA methylation mark in Sotos syndrome developed by nanopore sequencing-based episignature.","authors":"Takeshi Mizuguchi, Nobuhiko Okamoto, Taiki Hara, Naoto Nishimura, Masamune Sakamoto, Li Fu, Yuri Uchiyama, Naomi Tsuchida, Kohei Hamanaka, Eriko Koshimizu, Atsushi Fujita, Kazuharu Misawa, Kazuhiko Nakabayashi, Satoko Miyatake, Naomichi Matsumoto","doi":"10.1186/s13148-025-01832-0","DOIUrl":"10.1186/s13148-025-01832-0","url":null,"abstract":"<p><strong>Background: </strong>In various neurodevelopmental disorders (NDDs), sets of differential methylation marks (referred to as DNA methylation signatures or episignatures) are syndrome-specific and useful in evaluating the pathogenicity of detected genetic variants. These signatures have generally been tested using methylation arrays, requiring additional experimental and evaluation costs. As an alternative, long-read sequencing can simultaneously and accurately evaluate genetic and epigenetic changes. In addition, genome-wide DNA methylation profiling with more complete sets of CpG using long-read sequencing (than methylation arrays) may provide alternative but more comprehensive DNA methylation signatures, which have yet to be adequately investigated.</p><p><strong>Methods: </strong>Nine and seven cases of molecularly diagnosed Sotos syndrome and ATR-X syndrome, respectively, were sequenced using nanopore long-read sequencing, together with 22 controls. Genome-wide differential DNA methylation analysis was performed. Among these differential DNA methylation sites, a single-locus DNA methylation mark at part of the NSD1 CpG island (CpGi) was subsequently studied in an additional 22 cases with a NSD1 point mutation or a 5q35 submicroscopic deletion involving NSD1. To investigate the potential utility of a single-locus DNA methylation test at NSD1 CpGi for differential diagnosis, nine cases with NSD1-negative clinically overlapping overgrowth intellectual disability syndromes (OGIDs) were also tested.</p><p><strong>Results: </strong>Long-read sequencing enabled the successful extraction of two sets of differential methylation marks unique to each of Sotos syndrome and ATR-X syndrome, referred to as long-read-based DNA methylation signatures (LR-DNAm signatures), as alternatives to reported DNA methylation signatures (obtained by methylation array). Additionally, we found that a part, but not all, of the NSD1 CpGi were hypomethylated compared with the level in controls in both cases harboring NSD1 point mutations and those with a 5q35 submicroscopic deletion. This difference in methylation is specific to Sotos syndrome and lacking in other OGIDs.</p><p><strong>Conclusions: </strong>Simultaneous evaluation of genetic and epigenetic alterations using long-read sequencing may improve the discovery of DNA methylation signatures, which may in turn increase the diagnostic yields. As an example of the outcomes of these analyses, we propose that a single-locus DNA methylation test at NSD1 CpGi may streamline the molecular diagnosis of Sotos syndrome, regardless of the type of NSD1 aberration.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"27"},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448397","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":"LSD1 is a targetable vulnerability in gastric cancer harboring TP53 frameshift mutations.","authors":"Suzeng Wang, Chunyu Yang, Junhui Tang, Kaiqing Wang, Hao Cheng, Surui Yao, Zhaohui Huang, Bojian Fei","doi":"10.1186/s13148-025-01829-9","DOIUrl":"10.1186/s13148-025-01829-9","url":null,"abstract":"<p><strong>Background: </strong>TP53 mutations are linked to aggressive progression and chemoresistance in gastric cancer (GC). Frameshift mutation is the second most common mutation type of TP53. However, the consequences of this mutation type in GC were not well understood, and targeted therapies for cancer patients harboring frameshift mutations were also not established. Histone methylation significantly influences tumorigenesis in TP53-mutated cancers, and related inhibitors are emerging as specific therapeutic strategies.</p><p><strong>Methods and results: </strong>By treating GC cell lines harboring various TP53 mutation types with a library of histone demethylase inhibitors, we identified that GSK690, a reversible inhibitor of lysine-specific demethylase 1 (LSD1), selectively inhibits GC cells harboring TP53 frameshift mutations without nuclear localization sequence (NLS) (termed TP53 Frameshift <sup>NLS</sup>), which accounts for 89% TP53 frameshift mutations in GC patients. GSK690 showed significant specific inhibition in vitro and in vivo against this subtype by inducing G1/S cell cycle arrest via the LSD1-CCNA2 axis. Importantly, dual-luciferase assays and ChIP-qPCR confirmed that the loss of transcriptional repression activities of p53 in drives LSD1 upregulation in TP53 Frameshift <sup>NLS</sup> cancer cells.</p><p><strong>Conclusions: </strong>In summary, our results indicate that the nuclear localization deficiency of p53 accounts for increased expression of LSD1 in TP53 Frameshift <sup>NLS</sup> GCs. GSK690 inhibits cell cycle progression and tumor growth by suppressing aberrantly activated LSD1-CCNA2 signaling in this GC subtype, counteracting malignant proliferation and thereby providing a precise therapeutic strategy for GC patients with TP53 Frameshift <sup>NLS</sup>.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"26"},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448400","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}
Yoonsung Kwon, Asta Blazyte, Yeonsu Jeon, Yeo Jin Kim, Kyungwhan An, Sungwon Jeon, Hyojung Ryu, Dong-Hyun Shin, Jihye Ahn, Hyojin Um, Younghui Kang, Hyebin Bak, Byoung-Chul Kim, Semin Lee, Hyung-Tae Jung, Eun-Seok Shin, Jong Bhak
{"title":"Identification of 17 novel epigenetic biomarkers associated with anxiety disorders using differential methylation analysis followed by machine learning-based validation.","authors":"Yoonsung Kwon, Asta Blazyte, Yeonsu Jeon, Yeo Jin Kim, Kyungwhan An, Sungwon Jeon, Hyojung Ryu, Dong-Hyun Shin, Jihye Ahn, Hyojin Um, Younghui Kang, Hyebin Bak, Byoung-Chul Kim, Semin Lee, Hyung-Tae Jung, Eun-Seok Shin, Jong Bhak","doi":"10.1186/s13148-025-01819-x","DOIUrl":"10.1186/s13148-025-01819-x","url":null,"abstract":"<p><strong>Background: </strong>The changes in DNA methylation patterns may reflect both physical and mental well-being, the latter being a relatively unexplored avenue in terms of clinical utility for psychiatric disorders. In this study, our objective was to identify the methylation-based biomarkers for anxiety disorders and subsequently validate their reliability.</p><p><strong>Methods: </strong>A comparative differential methylation analysis was performed on whole blood samples from 94 anxiety disorder patients and 296 control samples using targeted bisulfite sequencing. Subsequent validation of identified biomarkers employed an artificial intelligence-based risk prediction models: a linear calculation-based methylation risk score model and two tree-based machine learning models: Random Forest and XGBoost.</p><p><strong>Results: </strong>Seventeen novel epigenetic methylation biomarkers were identified to be associated with anxiety disorders. These biomarkers were predominantly localized near CpG islands, and they were associated with two distinct biological processes: 1) cell apoptosis and mitochondrial dysfunction and 2) the regulation of neurosignaling. We further developed a robust diagnostic risk prediction system to classify anxiety disorders from healthy controls using the 17 biomarkers. Machine learning validation confirmed the robustness of our biomarker set, with XGBoost as the best-performing algorithm, an area under the curve of 0.876.</p><p><strong>Conclusion: </strong>Our findings support the potential of blood liquid biopsy in enhancing the clinical utility of anxiety disorder diagnostics. This unique set of epigenetic biomarkers holds the potential for early diagnosis, prediction of treatment efficacy, continuous monitoring, health screening, and the delivery of personalized therapeutic interventions for individuals affected by anxiety disorders.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"24"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440190","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}
Xiaoyu Deng, Peiran Li, Kaibing Tian, Fan Zhang, Yumeng Yan, Yanghua Fan, Zhen Wu, Junting Zhang, Jiang Du, Wei Chen, Liang Wang
{"title":"Radiogenomic method combining DNA methylation profiles and magnetic resonance imaging radiomics predicts patient prognosis in skull base chordoma.","authors":"Xiaoyu Deng, Peiran Li, Kaibing Tian, Fan Zhang, Yumeng Yan, Yanghua Fan, Zhen Wu, Junting Zhang, Jiang Du, Wei Chen, Liang Wang","doi":"10.1186/s13148-025-01836-w","DOIUrl":"10.1186/s13148-025-01836-w","url":null,"abstract":"<p><strong>Background: </strong>Chordoma is a rare malignant bone tumor exhibiting poor survival and prognosis. Hence, it is crucial to develop a convenient and effective prognostic classification method for the rehabilitation and management of patients with chordoma. In this study, we combined DNA methylation profiles and magnetic resonance imaging (MRI) images to generate a radiogenomic signature to assess its effectiveness for prognosis classification in patients with skull base chordoma.</p><p><strong>Results: </strong>DNA methylation profiles from chordoma tissue samples of 40 patients were factorized into eight DNA methylation signatures. Among them, Signature 4 was identified as the prognosis-specific signature. Based on the Signature 4 loading values, the patients were categorized into low-signature (LLG) and high-signature (HLG) loading groups. HLG patients had higher progression-free survival times than LLG patients. Combined analysis with external single-cell RNA-seq data revealed higher tumor cell proportions and lower natural killer cell proportions in the HLG than in the LLG. Additionally, 2,553 radiomic features were extracted from T1, T2, and enhanced T1 MRI images of the patients, and a radiogenomic signature comprising 14 radiomic features was developed. In a validation cohort of 122 patients, the radiogenomic signature successfully distinguished between the two groups (P = 0.027). Furthermore, the existence of Signature 4 was confirmed in an additional dataset of 14 patients.</p><p><strong>Conclusion: </strong>We developed a prognostic radiogenomic signature using a radiogenomic classification method, which leverages MRI images to extract features that reflect the DNA methylation signature associated with prognosis, enabling the stratification of patients based on their prognostic risk. This method offers the advantages of being noninvasive and convenient.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"23"},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440193","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}