Epigenetics最新文献_第4页

Global DNA methylation is not elevated in blood samples from Machado-Joseph disease mutation carriers. 在马查多-约瑟夫病突变携带者的血液样本中，全局 DNA 甲基化没有升高。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-06-20 DOI: 10.1080/15592294.2024.2368995

Luís Teves, Ana Rosa Vieira Melo, Ana F Ferreira, Mafalda Raposo, Carolina Lemos, Conceição Bettencourt, Manuela Lima

{"title":"Global DNA methylation is not elevated in blood samples from Machado-Joseph disease mutation carriers.","authors":"Luís Teves, Ana Rosa Vieira Melo, Ana F Ferreira, Mafalda Raposo, Carolina Lemos, Conceição Bettencourt, Manuela Lima","doi":"10.1080/15592294.2024.2368995","DOIUrl":"10.1080/15592294.2024.2368995","url":null,"abstract":"Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia (SCA) caused by a polyglutamine expansion in the ataxin-3 protein, which initiates a cascade of pathogenic events, including transcriptional dysregulation. Genotype-phenotype correlations in MJD are incomplete, suggesting an influence of additional factors, such as epigenetic modifications, underlying the MJD pathogenesis. DNA methylation is known to impact the pathophysiology of neurodegenerative disorders through gene expression regulation and increased methylation has been reported for other SCAs. In this work we aimed to analyse global methylation in MJD carriers. Global 5-mC levels were quantified in blood samples of 33 MJD mutation carriers (patients and preclinical subjects) and 33 healthy controls, matched by age, sex, and smoking status. For a subset of 16 MJD subjects, a pilot follow-up analysis with two time points was also conducted. No differences were found in median global 5-mC levels between MJD mutation carriers and controls and no correlations between methylation levels and clinical or genetic variables were detected. Also, no alterations in global 5-mC levels were observed over time. Our findings do not support an increase in global blood methylation levels associated with MJD.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2368995"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors. 药物治疗后 HDAC 和 SIRT 基因表达的变化与癌细胞系对激酶抑制剂敏感性的关系。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-02-18 DOI: 10.1080/15592294.2024.2309824

Julia Krushkal, Yingdong Zhao, Kyle Roney, Weimin Zhu, Alan Brooks, Deborah Wilsker, Ralph E Parchment, Lisa M McShane, James H Doroshow

{"title":"Association of changes in expression of HDAC and SIRT genes after drug treatment with cancer cell line sensitivity to kinase inhibitors.","authors":"Julia Krushkal, Yingdong Zhao, Kyle Roney, Weimin Zhu, Alan Brooks, Deborah Wilsker, Ralph E Parchment, Lisa M McShane, James H Doroshow","doi":"10.1080/15592294.2024.2309824","DOIUrl":"10.1080/15592294.2024.2309824","url":null,"abstract":"Histone deacetylases (HDACs) and sirtuins (SIRTs) are important epigenetic regulators of cancer pathways. There is a limited understanding of how transcriptional regulation of their genes is affected by chemotherapeutic agents, and how such transcriptional changes affect tumour sensitivity to drug treatment. We investigated the concerted transcriptional response of HDAC and SIRT genes to 15 approved antitumor agents in the NCI-60 cancer cell line panel. Antitumor agents with diverse mechanisms of action induced upregulation or downregulation of multiple HDAC and SIRT genes. HDAC5 was upregulated by dasatinib and erlotinib in the majority of the cell lines. Tumour cell line sensitivity to kinase inhibitors was associated with upregulation of HDAC5, HDAC1, and several SIRT genes. We confirmed changes in HDAC and SIRT expression in independent datasets. We also experimentally validated the upregulation of HDAC5 mRNA and protein expression by dasatinib in the highly sensitive IGROV1 cell line. HDAC5 was not upregulated in the UACC-257 cell line resistant to dasatinib. The effects of cancer drug treatment on expression of HDAC and SIRT genes may influence chemosensitivity and may need to be considered during chemotherapy.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2309824"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma. 血浆甲基化 GNB4 和 Riplet 作为检测肝细胞癌的新型双标记物面板。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2023-12-28 DOI: 10.1080/15592294.2023.2299044

Yanteng Zhao, Lei Zhao, Huifang Jin, Ying Xie, Liyinghui Chen, Wei Zhang, Lanlan Dong, Lianglu Zhang, Yue Huang, Kangkang Wan, Qiankun Yang, Shaochi Wang

{"title":"Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma.","authors":"Yanteng Zhao, Lei Zhao, Huifang Jin, Ying Xie, Liyinghui Chen, Wei Zhang, Lanlan Dong, Lianglu Zhang, Yue Huang, Kangkang Wan, Qiankun Yang, Shaochi Wang","doi":"10.1080/15592294.2023.2299044","DOIUrl":"10.1080/15592294.2023.2299044","url":null,"abstract":"Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals). The combination of G protein subunit beta 4 (GNB4) and Riplet had the optimal area under the curve (AUC) in seven candidates through TCGA, GEO, and WGBS analyses. In tissue validation, the GNB4 and Riplet showed an AUC of 100% with a sensitivity and specificity of 100% for detecting any-stage HCC. In plasma, it demonstrated a high sensitivity of 84.39% at 91.92% specificity, with an AUC of 92.51% for detecting any-stage HCC. The dual-marker panel had a higher sensitivity of 78.26% for stage I HCC than alpha-fetoprotein (AFP) of 47.83%, and a high sensitivity of 70.27% for detecting a single tumour (size ≤3 cm). In conclusion, we developed a novel dual-marker panel that demonstrates high accuracy in detecting HCC, surpassing the performance of AFP testing.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2299044"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome. ZSCAN25 甲基化可预测癫痫发作和严重酒精戒断综合征。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-01-03 DOI: 10.1080/15592294.2023.2298057

Allan Andersen, Emily Milefchik, Emma Papworth, Brandan Penaluna, Kelsey Dawes, Joanna Moody, Gracie Weeks, Ellyse Froehlich, Kaitlyn deBlois, Jeffrey D Long, Robert Philibert

{"title":"ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome.","authors":"Allan Andersen, Emily Milefchik, Emma Papworth, Brandan Penaluna, Kelsey Dawes, Joanna Moody, Gracie Weeks, Ellyse Froehlich, Kaitlyn deBlois, Jeffrey D Long, Robert Philibert","doi":"10.1080/15592294.2023.2298057","DOIUrl":"10.1080/15592294.2023.2298057","url":null,"abstract":"Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (ZSCAN25) and CDT strongly predicted severe AWS with ATS (p < 0.007) and cg07375256 (p < 6 × 10-5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2298057"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10766392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139080447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex and tissue-specificity of piRNA regulation in adult mice following perinatal lead (Pb) exposure. 围产期铅（Pb）暴露后成年小鼠 piRNA 调节的性别和组织特异性。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1080/15592294.2024.2426952

Bambarendage P U Perera, Kai Wang, Dongyue Wang, Kathleen Chen, Alisa Dewald, Swati Sriram, Jaclyn M Goodrich, Laurie K Svoboda, Maureen A Sartor, Dana C Dolinoy

{"title":"Sex and tissue-specificity of piRNA regulation in adult mice following perinatal lead (Pb) exposure.","authors":"Bambarendage P U Perera, Kai Wang, Dongyue Wang, Kathleen Chen, Alisa Dewald, Swati Sriram, Jaclyn M Goodrich, Laurie K Svoboda, Maureen A Sartor, Dana C Dolinoy","doi":"10.1080/15592294.2024.2426952","DOIUrl":"10.1080/15592294.2024.2426952","url":null,"abstract":"Lead (Pb) is a neurotoxicant with early life exposure linked to long-term health effects. Piwi-interacting RNAs (piRNAs) are small non-coding RNAs that associate with PIWIL proteins to induce DNA methylation. It remains unknown whether Pb exposure influences piRNA expression. This study evaluated how perinatal Pb exposure (32 ppm in drinking water) impacts piRNA expression in adult mice and assessed piRNA dysregulation as a potential mechanism for Pb-induced toxicity. Pb exposure effects on piRNA expression and associated gene repression in the germline (testis/ovary) and soma (liver and brain) were evaluated. Small RNA sequencing was used to determine differentially expressed piRNAs, RT-qPCR to examine piRNA target expression, and whole genome bisulfite sequencing to evaluate target DNA methylation status. Three piRNAs (mmpiR-1500602, mmpiR-0201406, and mmpiR-0200026) were significant after multiple testing correction (all downregulated in the male Pb-exposed brain in comparison to control; FDR < 0.05). Within piOxiDB, TAO Kinase 3 was identified as a downstream mRNA target for one of the three Pb-sensitive piRNA. The Pb-exposed male brain exhibited increased Taok3 expression (p < 0.05) and decreased DNA methylation (FDR < 0.01). The results demonstrate that perinatal Pb exposure stably influences longitudinal piRNA expression in a tissue- and sex-specific manner, potentially via DNA methylation-directed mechanisms.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2426952"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Letter to the editor: critical evaluation of the reliability of DNA methylation probes on the illumina MethylationEPIC v1.0 BeadChip microarrays. 致编辑的信：对illumina MethylationEPIC v1.0 BeadChip芯片上DNA甲基化探针可靠性的批判性评估。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-10-04 DOI: 10.1080/15592294.2024.2411470

Julian Hecker, Scott T Weiss, Jessica A Lasky-Su, Dawn L DeMeo, Christoph Lange

引用次数: 0

Epigenome-wide association study of loneliness in a sample of U.S. middle-aged twins. 美国中年双胞胎孤独感的全表观基因组关联研究。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-12-08 DOI: 10.1080/15592294.2024.2427999

Christopher R Beam, Kelly M Bakulski, Ebrahim Zandi, Eric Turkheimer, Morgan Lynch, Alaina I Gold, Thalida Em Arpawong, Sophie A Bell, Alyssa C Kam, Jonathan Becker, Deborah Winders Davis

{"title":"Epigenome-wide association study of loneliness in a sample of U.S. middle-aged twins.","authors":"Christopher R Beam, Kelly M Bakulski, Ebrahim Zandi, Eric Turkheimer, Morgan Lynch, Alaina I Gold, Thalida Em Arpawong, Sophie A Bell, Alyssa C Kam, Jonathan Becker, Deborah Winders Davis","doi":"10.1080/15592294.2024.2427999","DOIUrl":"10.1080/15592294.2024.2427999","url":null,"abstract":"Loneliness is a complex human trait that is highly polygenic and found to affect gene expression related to inflammatory and immunological functioning. To date, no epigenome-wide association studies of loneliness have tested whether differentially methylated sites are annotated to genes associated with inflammatory and immunological processes. Using 281 individual adult twins' DNA methylation data from the Louisville Twin Study, we performed an epigenome-wide analysis of loneliness to address this gap in the literature. In the discovery analysis, 169 twins were used to prioritize probes and test associations with DNA methylation age acceleration, and 56 independent monozygotic (MZ) twin pairs (112 individuals) were used in a within-family replication analysis. Among the 837,274 sites analyzed, no probe sites were statistically significant at the genome-wide level (p < 5.97 × 10-8), but 25 suggestive sites (p < 5 × 10-5) were annotated to genes related to various biological processes, including inflammatory response and protein-binding functions that extend prior findings. The nominal associations at these suggestive probe sites were highly correlated (r = .72) between the discovery sample and the MZ pair replication sample. Finally, loneliness significantly correlated with the DunedinPACE DNA methylation measure, suggesting that higher levels of loneliness were associated with accelerated epigenetic age as quantified by a measure that indexes longitudinal changes across multiple organ systems.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2427999"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A promising application of kidney-specific cell-free DNA methylation markers in real-time monitoring sepsis-induced acute kidney injury. 肾脏特异性无细胞 DNA 甲基化标记在实时监测败血症诱发的急性肾损伤中的应用前景广阔。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-10-07 DOI: 10.1080/15592294.2024.2408146

Ruilian You, Xiangming Quan, Peng Xia, Chao Zhang, Anlei Liu, Hanshu Liu, Ling Yang, Huadong Zhu, Limeng Chen

{"title":"A promising application of kidney-specific cell-free DNA methylation markers in real-time monitoring sepsis-induced acute kidney injury.","authors":"Ruilian You, Xiangming Quan, Peng Xia, Chao Zhang, Anlei Liu, Hanshu Liu, Ling Yang, Huadong Zhu, Limeng Chen","doi":"10.1080/15592294.2024.2408146","DOIUrl":"10.1080/15592294.2024.2408146","url":null,"abstract":"Sepsis-induced acute kidney injury (SI-AKI) is a common clinical syndrome that is associated with high mortality and morbidity. Effective timely detection may improve the outcome of SI-AKI. Kidney-derived cell-free DNA (cfDNA) may provide new insight into understanding and identifying SI-AKI. Plasma cfDNA from 82 healthy individuals, 7 patients with sepsis non-acute kidney injury (SN-AKI), and 9 patients with SI-AKI was subjected to genomic methylation sequencing. We deconstructed the relative contribution of cfDNA from different cell types based on cell-specific methylation markers and focused on exploring the association between kidney-derived cfDNA and SI-AKI.Based on the deconvolution of the cfDNA methylome: SI-AKI patients displayed the elevated cfDNA concentrations with an increased contribution of kidney epithelial cells (kidney-Ep) DNA; kidney-Ep derived cfDNA achieved high accuracy in distinguishing SI-AKI from SN-AKI (AUC = 0.92, 95% CI 0.7801-1); the higher kidney-ep cfDNA concentrations tended to correlate with more advanced stages of SI-AKI; strikingly, SN-AKI patients with potential kidney damage unmet by SI-AKI criteria showed higher levels of kidney-Ep derived cfDNA than healthy individuals. The autonomous screening of kidney-Ep (n = 24) and kidney endothelial (kidney-Endo, n = 12) specific methylation markers indicated the unique identity of kidney-Ep/kidney-Endo compared with other cell types, and its targeted assessment reproduced the main findings of the deconvolution of the cfDNA methylome. Our study first demonstrates that kidney-Ep- and kidney-Endo-specific methylation markers can serve as a novel marker for SI-AKI emergence, supporting further exploration of the utility of kidney-specific cfDNA methylation markers in the study of SI-AKI.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2408146"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Observational methods for human studies of transgenerational effects. 人类跨代效应研究的观察方法。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-06-13 DOI: 10.1080/15592294.2024.2366065

Rebecca Richards-Steed, Neng Wan, Amanda Bakian, Richard M Medina, Simon C Brewer, Ken R Smith, James A VanDerslice

{"title":"Observational methods for human studies of transgenerational effects.","authors":"Rebecca Richards-Steed, Neng Wan, Amanda Bakian, Richard M Medina, Simon C Brewer, Ken R Smith, James A VanDerslice","doi":"10.1080/15592294.2024.2366065","DOIUrl":"10.1080/15592294.2024.2366065","url":null,"abstract":"There are substantial challenges in studying human transgenerational epigenetic outcomes resulting from environmental conditions. The task requires specialized methods and tools that incorporate specific knowledge of multigenerational relationship combinations of probands and their ancestors, phenotype data for individuals, environmental information of ancestors and their descendants, which can span historical to present datasets, and informative environmental data that chronologically aligns with ancestors and descendants over space and time. As a result, there are few epidemiologic studies of potential transgenerational effects in human populations, thus limiting the knowledge of ancestral environmental conditions and the potential impacts we face with modern human health outcomes. In an effort to overcome some of the challenges in studying human transgenerational effects, we present two transgenerational study designs: transgenerational space-time cluster detection and transgenerational case-control study design. Like other epidemiological methods, these methods determine whether there are statistical associations between phenotypic outcomes (e.g., adverse health outcomes) among probands and the shared environments and environmental factors facing their ancestors. When the ancestor is a paternal grandparent, a statistically significant association provides some evidence that a transgenerational inheritable factor may be involved. Such results may generate useful hypotheses that can be explored using epigenomic data to establish conclusive evidence of transgenerational heritable effects. Both methods are proband-centric: They are designed around the phenotype of interest in the proband generation for case selection and family pedigree creation. In the examples provided, we incorporate at least three generations of paternal lineage in both methods to observe a potential transgenerational effect.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2366065"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11178273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL21R hypomethylation as a biomarker for distinguishing benign and malignant breast tumours. IL21R 低甲基化是区分良性和恶性乳腺肿瘤的生物标记物。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-05-09 DOI: 10.1080/15592294.2024.2352683

Zishan Zang, Yifei Yin, Chunlan Liu, Qiang Zhu, Xuandong Huang, Hong Li, Rongxi Yang

{"title":"IL21R hypomethylation as a biomarker for distinguishing benign and malignant breast tumours.","authors":"Zishan Zang, Yifei Yin, Chunlan Liu, Qiang Zhu, Xuandong Huang, Hong Li, Rongxi Yang","doi":"10.1080/15592294.2024.2352683","DOIUrl":"10.1080/15592294.2024.2352683","url":null,"abstract":"Some benign and malignant breast tumours are similar in pathological morphology, which are difficult to be distinguished in clinical diagnosis. In this study, we intended to explore novel biomarkers for differential diagnosis of benign and malignant breast tumours. Methylation EPIC 850K beadchip and RNA-sequencing were used to analyse 29 tissue samples from patients with early-stage breast cancer (BC) and benign breast tumours for differently methylated and expressed genes. The altered methylation of IL21R was semi-quantitatively validated in an independent study with 566 tissue samples (279 BC vs. 287 benign breast tumours) using mass spectrometry. Binary logistic regression analysis was performed to evaluate the association between IL21R methylation and BC. BC-associated IL21R hypomethylation and overexpression were identified in the discovery round. In the validation round, BC patients presented significant IL21R hypomethylation compared to women with benign breast tumours (ORs ≥1.29 per-10% methylation, p-values ≤ 5.69E-14), and this hypomethylation was even enhanced in BC patients with ER-negative and PR-negative tumours as well as with triple-negative tumours. The methylation of IL21R showed efficient discriminatory power to distinguish benign breast tumours from BC (area under curve (AUC) = 0.88), and especially from ER-negative BC (AUC = 0.95), PR-negative BC (AUC = 0.93) and triple-negative BC (AUC = 0.96). We disclosed significant IL21R hypomethylation in patients with BC compared to women with benign breast tumours, and revealed the somatic change of DNA methylation could be a potential biomarker for molecular pathology of BC.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2352683"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0