Clinical Epigenetics最新文献

{"title":"Plasma cfDNA VILL gene methylation as a diagnostic marker for nasopharyngeal carcinoma.","authors":"Xiao-Yan Fu, Zi-Ying Zhou, Teng-Yue Yang, Ying-Juan Wen, Da-Bo Liu, Yi-Bo Zhou, Yuan Yue, Fei Ye, Zhong-Xi Huang","doi":"10.1186/s13148-025-01847-7","DOIUrl":"10.1186/s13148-025-01847-7","url":null,"abstract":"<p><p>Currently, the non-invasive diagnostic methods for nasopharyngeal carcinoma (NPC) continue to grapple with the challenge of low sensitivity. The hypermethylation of tumor suppressor genes is an established early event in NPC pathogenesis. Consequently, we conducted whole-genome methylation sequencing on plasma cell-free DNA (cfDNA) from six NPC cases and four healthy controls, integrating Illumina Human Methylation 450 K microarray data from the GEO database comprising six NPC cases and six samples of non-cancerous nasopharyngeal tissue (NP). As result, we screened only one CpG island associated with cell type-specific regulation within the candidate tumor suppressor gene VILL (Vilin Like), which exhibits specific methylation patterns in NPC. We validated our findings using 25 pairs of NPC and NP samples from GEO, alongside 9,736 pan-cancer tissues from TCGA and 656 healthy human leukocyte samples sourced from GEO through methylation microarray analysis. Based on this, we designed a methylation-specific qPCR (qMSP) system for the VILL gene, and then tested it on 192 primary NPC and 154 NC plasma samples. The new qMSP system when compared with EBV DNA qPCR revealed a sensitivity for primary NPC of 80.2% vs.81.3% (78.8% vs.54.5% for early-stage NPC), and a specificity of 100% vs. 93.5%. Notably, employing a combined methodology further enhanced sensitivity to 94.8%, including a sensitivity rate of 90.9% for early-stage NPC diagnosis. Therefore, VILL methylation assessment combined with EBV DNA detection presents a promising avenue for non-invasive diagnosis of NPC, particularly beneficial for early detection.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"38"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522743","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":"HDAC inhibitors modulate Hippo pathway signaling in hormone positive breast cancer.","authors":"Ting-I Lin, Yi-Ru Tseng, Min-Jyun Dong, Chih-Yi Lin, Wei-Ting Chung, Chun-Yu Liu, Yi-Fang Tsai, Chi-Cheng Huang, Ling-Ming Tseng, Ta-Chung Chao, Jiun-I Lai","doi":"10.1186/s13148-025-01834-y","DOIUrl":"10.1186/s13148-025-01834-y","url":null,"abstract":"<p><p>Breast cancer has constantly been the leading causes of death in women, and hormone receptor (HR) positive, HER2 negative is the majority subtype. Histone deacetylase (HDAC) inhibitors (HDACi) have shown clinical benefit in HR ( +) breast cancer patients. The Hippo pathway is an important cellular pathway involving proliferation, cell contact, and cancer. Hippo pathway proteins YAP/TAZ are often viewed as pro-tumorigenic; however, recent studies support a role of YAP as a tumor suppressor in HR ( +) breast cancer. Few studies have investigated the link between HDACi and the Hippo pathway. In our study, we demonstrate that HDACi induces transcriptional downregulation of YAP expression, while conversely activating a TEAD-mediated transcriptional program with upregulation of canonical Hippo pathway genes. We subsequently identified four Hippo canonical genes (CCDC80, GADD45A, F3, and TGFB2) that were upregulated by HDACi and associated with significantly improved survival in a HR ( +) breast cancer cohort. We further validated experimentally that HR ( +) breast cancer cells treated with HDACi resulted in upregulation of CCDC80 and GADD45A. A pan-cancer analysis of TCGA database demonstrated lower CCDC80 and GADD45A expression in tumor tissue compared to non-tumor samples in BRCA (breast cancer), LAML (acute myeloid leukemia), and UCS (uterine carcinosarcoma). Further analysis of HR ( +) breast cancer patients in the METABRIC dataset revealed high CCDC80 and/or GADD45A expression associated with significantly better survival outcomes compared to patients with low expression. Our study provides evidence for a novel mechanism of HDACi clinical activity, as well as a potential role for CCDC80 and GADD45A in HR ( +) breast cancer.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"37"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514914","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":"Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional [⁶⁸Ga]Ga-PSMA-11 PET/CT study.","authors":"Kilian Kluge, Vincent Lotz, Holger Einspieler, David Haberl, Clemens Spielvogel, Dominik Amereller, Gero Kramer, Bernhard Grubmüller, Shahrokh Shariat, Alexander Haug, Marcus Hacker, Lukas Kenner, Gerda Egger","doi":"10.1186/s13148-025-01811-5","DOIUrl":"10.1186/s13148-025-01811-5","url":null,"abstract":"<p><strong>Background: </strong>To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa).</p><p><strong>Methods: </strong>122 PCa patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried. PET scans were qualitatively and quantitatively assessed. PSA and meth-ctDNA markers were compared to PET findings, and their relative prognostic value was evaluated.</p><p><strong>Results: </strong>PSA discriminated best between negative and tumor-indicative PET scans in all (AUC 0.77) and hormone-sensitive (hsPC) patients (0.737). In castration-resistant PCa (CRPC), the meth-ctDNA marker KLF8 performed best (AUC 0.824). CHST11 differentiated best between non- and metastatic scans (AUC 0.705) overall, KLF8 best in hsPC and CRPC (AUC 0.662, 0.85). Several meth-ctDNA markers correlated low to moderate with the tumor volume in all (5/8) and CRPC patients (6/8), while PSA levels correlated moderately to strongly with the tumor volume in all groups (all p < 0.001). CRPC overall survival was independently associated with LDAH and PSA (p = 0.0168, p < 0.001).</p><p><strong>Conclusion: </strong>The studied meth-ctDNA markers are promising for the minimally-invasive detection and prognostication of CRPC but do not allow for clinical characterization of hsPC. Prospective studies are warranted for their use in therapy response and outcome prediction in CRPC and potential incremental value for PCa monitoring in PSA-low settings.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"36"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499528","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":"Roles and mechanisms of histone methylation in vascular aging and related diseases.","authors":"Yufei Ji, Zhenzhen Chen, Jun Cai","doi":"10.1186/s13148-025-01842-y","DOIUrl":"10.1186/s13148-025-01842-y","url":null,"abstract":"<p><p>The global aging trend has posed significant challenges, rendering healthcare for older adults a crucial focus in medical research. Among the numerous health concerns related to aging, vascular aging and dysfunction are important risk factors and underlying causes of age-related diseases. Histone methylation and demethylation, which are involved in gene expression and cellular senescence, are closely associated with the occurrence and development of vascular aging. Consequently, this review aimed to identify the role of histone methylation in the pathogenesis of vascular aging and its potential for treating age-related vascular diseases and provided new insights into therapeutic strategies targeting the vascular system.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"35"},"PeriodicalIF":4.8,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482305","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":"Black community member perceptions and ethics recommendations on epigenomic research.","authors":"Courtney Berrios, Tammy Basey, Andrea Bradley-Ewing, Stacey Daniels-Young, Daysha Lewis, Keith Feldman, Mary E Moffatt, Tomi Pastinen, Elin Grundberg","doi":"10.1186/s13148-025-01840-0","DOIUrl":"10.1186/s13148-025-01840-0","url":null,"abstract":"<p><strong>Background: </strong>Social epigenomics research investigates links between social experiences and epigenetic modifications, which may ultimately impact health. Such research holds promise for precision medicine and addressing health disparities based on social conditions, but also brings unique ethical challenges. The linking of social experiences to biological changes risks pathologizing experiences, potentially leading individuals and communities to be seen as 'damaged.' This stigmatization or stereotyping based on experiences also risks placing disproportionate personal responsibility for health. These risks are likely to be amplified in historically marginalized communities already facing discrimination. It is therefore essential to engage members of historically marginalized communities to explore attitudes about social epigenomics research. This study focuses on the Black and African American (B/AA) population in the USA, studying perceptions of social epigenomic research participants, research decliners, and broadly representative community members to identify perceived benefits and risks of social epigenomic research as well as strategies to maximize benefits and lower risks for both participants and communities.</p><p><strong>Results: </strong>Both research participants and community members perceived potential benefit of social epigenomic research for the B/AA population. While most research participants did not perceive research related risks, community members identified risks both specific to social epigenomic research and more generalized to medical research. Several of the risks identified, and a belief that the likelihood of harms was greater than the likelihood of benefits, were based on past research injustices to B/AA research participants and mistrust in the medical and research enterprise. However, community members provided concrete strategies for maximizing the chance of benefits and lowering risk of harms including acknowledging and addressing biases and past injustices, ensuring transparency and understanding, positive framing of research, thorough research and dissemination, and engaging with communities before, throughout, and beyond the research process.</p><p><strong>Conclusions: </strong>While B/AA community members identified risk of both individual and community harm from social epigenomic research, they also perceived potential health benefits for the B/AA community. Through concerted efforts to apply community recommendations to lower risks and enhance benefits, researchers can conduct ethical and valid epigenomic research that aims to address health disparities with historically marginalized communities.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"33"},"PeriodicalIF":4.8,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476310","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 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}

{"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}

{"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}

{"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}