{"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":"<p><p>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 (<i>n</i> = 24) and kidney endothelial (kidney-Endo, <i>n</i> = 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.</p>","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-06-13DOI: 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":"<p><p>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.</p>","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-05-09DOI: 10.1080/15592294.2024.2352683
Zishan Zang, Yifei Yin, Chunlan Liu, Qiang Zhu, Xuandong Huang, Hong Li, Rongxi Yang
{"title":"<i>IL21R</i> 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":"<p><p>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 <i>IL21R</i> 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 <i>IL21R</i> methylation and BC. BC-associated <i>IL21R</i> hypomethylation and overexpression were identified in the discovery round. In the validation round, BC patients presented significant <i>IL21R</i> hypomethylation compared to women with benign breast tumours (ORs ≥1.29 per-10% methylation, <i>p-</i>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 <i>IL21R</i> 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 <i>IL21R</i> 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.</p>","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}
{"title":"Integration of miRNA expression analysis of purified leukocytes and whole blood reveals blood-borne candidate biomarkers for lung cancer.","authors":"Guini Hong, Yue Huo, Yaru Gao, Liyuan Ma, Shuang Li, Tian Tian, Haijian Zhong, Hongdong Li","doi":"10.1080/15592294.2024.2393948","DOIUrl":"10.1080/15592294.2024.2393948","url":null,"abstract":"<p><p>Changes in leukocyte populations may confound the disease-associated miRNA signals in the blood of cancer patients. We aimed to develop a method to detect differentially expressed miRNAs from lung cancer whole blood samples that are not influenced by variations in leukocyte proportions. The Ref-miREO method identifies differential miRNAs unaffected by changes in leukocyte populations by comparing the within-sample relative expression orderings (REOs) of miRNAs from healthy leukocyte subtypes and those from lung cancer blood samples. Over 77% of the differential miRNAs observed between lung cancer and healthy blood samples overlapped with those between myeloid-derived and lymphoid-derived leukocytes, suggesting the potential impact of changes in leukocyte populations on miRNA profile. Ref-miREO identified 16 differential miRNAs that target 19 lung adenocarcinoma-related genes previously linked to leukocytes. These miRNAs showed enrichment in cancer-related pathways and demonstrated high potential as diagnostic biomarkers, with the LASSO regression models effectively distinguishing between healthy and lung cancer blood or serum samples (all AUC > 0.85). Additionally, 12 of these miRNAs exhibited significant prognostic correlations. The Ref-miREO method offers valuable candidates for circulating biomarker detection in cancer that are not affected by changes in leukocyte populations.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2393948"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008522","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2023-12-25DOI: 10.1080/15592294.2023.2298058
Jie Lai, Zhiyong Zhou, Kan Hu, HongLong Yu, Xingyao Su, Xiaoqiang Niu, Huizi Li, Shengxun Mao
{"title":"N6-methyladenosine methylation analysis of long noncoding RNAs and mRNAs in 5-FU-resistant colon cancer cells.","authors":"Jie Lai, Zhiyong Zhou, Kan Hu, HongLong Yu, Xingyao Su, Xiaoqiang Niu, Huizi Li, Shengxun Mao","doi":"10.1080/15592294.2023.2298058","DOIUrl":"10.1080/15592294.2023.2298058","url":null,"abstract":"<p><p>N6 methyladenosine (m6A), methylation at the sixth N atom of adenosine, is the most common and abundant modification in mammalian mRNAs and non-coding RNAs. Increasing evidence shows that the alteration of m6A modification level could regulate tumour proliferation, metastasis, self-renewal, and immune infiltration by regulating the related expression of tumour genes. However, the role of m6A modification in colorectal cancer (CRC) drug resistance is unclear. Here, MeRIP-seq and RNA-seq techniques were utilized to obtain mRNA, lncRNA expression, and their methylation profiles in 5-Fluorouracil (5-FU)-resistant colon cancer HCT-15 cells and control cells. In addition, we performed detailed bioinformatics analysis as well as in vitro experiments of lncRNA to explore the function of lncRNA with differential m6A in CRC progression and drug resistance. In this study, we obtained the m6A methylomic landscape of CRC cells and resistance group cells by MeRIP-seq and RNA-seq. We identified 3698 differential m6A peaks, of which 2224 were hypermethylated, and 1474 were hypomethylated. Among the lncRNAs, 60 were hypermethylated, and 38 were hypomethylated. GO and KEGG analysis annotations showed significant enrichment of endocytosis and MAPK signalling pathways. Moreover, knockdown of lncRNA ADIRF-AS1 and AL139035.1 promoted CRC proliferation and invasive metastasis in vitro. lncRNA- mRNA network showed that ADIRF-AS1 and AL139035.1 May play a key role in regulating drug resistance formation. We provide the first m6A methylation profile in 5-FU resistance CRC cells and analyse the functions of differential m6A-modified mRNAs and lncRNAs. Our results indicated that differential m6A RNAs were significantly associated with MAPK signalling and endocytosis after induction of 5-FU resistance. Knockdown of LncRNA ADIRF-AS1 and AL139035.1 promotes CRC progression and might be critical in regulating drug resistance formation.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2298058"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037538","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-10-03DOI: 10.1080/15592294.2024.2408843
Fei-Man Hsu, Rashmi P Mohanty, Liudmilla Rubbi, Michael Thompson, Harry Pickering, Elaine F Reed, John R Greenland, Joanna M Schaenman, Matteo Pellegrini
{"title":"An epigenetic human cytomegalovirus infection score predicts viremia risk in seropositive lung transplant recipients.","authors":"Fei-Man Hsu, Rashmi P Mohanty, Liudmilla Rubbi, Michael Thompson, Harry Pickering, Elaine F Reed, John R Greenland, Joanna M Schaenman, Matteo Pellegrini","doi":"10.1080/15592294.2024.2408843","DOIUrl":"10.1080/15592294.2024.2408843","url":null,"abstract":"<p><p>Cytomegalovirus (CMV) infection and reactivation in solid organ transplant (SOT) recipients increases the risk of viremia, graft failure and death. Clinical studies of CMV serostatus indicate that donor positive recipient negative (D<sup>+</sup>/R<sup>-</sup>) patients have greater viremia risk than D<sup>-</sup>/R<sup>-</sup>. The majority of patients are R<sup>+</sup> having intermediate serologic risk. To characterize the long-term impact of CMV infection and assess viremia risk, we sought to measure the effects of CMV on the recipient immune epigenome. Specifically, we profiled DNA methylation in 156 individuals before lung or kidney transplant. We found that the methylome of CMV positive SOT recipients is hyper-methylated at <i>loci</i> associated with neural development and Polycomb group (PcG) protein binding, and hypo-methylated at regions critical for the maturation of lymphocytes. In addition, we developed a machine learning-based model to predict the recipient CMV serostatus after correcting for cell type composition and ancestry. This CMV episcore measured at baseline in R<sup>+</sup> individual stratifies viremia risk accurately in the lung transplant cohort, and along with serostatus the CMV episcore could be a potential biomarker for identifying R<sup>+</sup> patients at high viremia risk.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2408843"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364900","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-08-16DOI: 10.1080/15592294.2024.2391602
Lotfi Bouzeraa, Helene Martin, Clement Plessis, Pascal Dufour, Jessica C S Marques, Sydney Moore, Ronaldo Cerri, Marc-Andre Sirard
{"title":"Decoding epigenetic markers: implications of traits and genes through DNA methylation in resilience and susceptibility to mastitis in dairy cows.","authors":"Lotfi Bouzeraa, Helene Martin, Clement Plessis, Pascal Dufour, Jessica C S Marques, Sydney Moore, Ronaldo Cerri, Marc-Andre Sirard","doi":"10.1080/15592294.2024.2391602","DOIUrl":"10.1080/15592294.2024.2391602","url":null,"abstract":"<p><p>Cattle farming faces challenges linked to intensive exploitation and climate change, requiring the reinforcement of animal resilience in response to these dynamic environments. Currently, genetic selection is used to enhance resilience by identifying animals resistant to specific diseases; however, certain diseases, such as mastitis, pose difficulties in genetic prediction. This study introduced the utilization of enzymatic methyl sequencing (EM-seq) of the blood genomic DNA from twelve dairy cows to identify DNA methylation biomarkers, with the aim of predicting resilience and susceptibility to mastitis. The analysis uncovered significant differences between cows resilient and susceptible to mastitis, with 196,275 differentially methylated cytosines (DMCs) and 1,227 Differentially Methylated Regions (DMRs). Key genes associated with the immune response and morphological traits, including ENOPH1, MYL10 and KIR2DL5A, were identified by our analysis. Quantitative trait loci (QTL) were also highlighted and the body weight trait was the most targeted by DMCs and DMRs. Based on our results, the risk of developing mastitis can potentially be estimated with as few as fifty methylation biomarkers, paving the way for early animal selection. This research sets the stage for improved animal health management and economic yields within the framework of agricultural sustainability through early selection based on the epigenetic status of animals.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2391602"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992222","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-09-01DOI: 10.1080/15592294.2024.2397297
Joanna Ciantar, Saara Marttila, Sonja Rajić, Daria Kostiniuk, Pashupati P Mishra, Leo-Pekka Lyytikäinen, Nina Mononen, Marcus E Kleber, Winfried März, Mika Kähönen, Olli Raitakari, Terho Lehtimäki, Emma Raitoharju
{"title":"Identification and functional characterisation of DNA methylation differences between East- and West-originating Finns.","authors":"Joanna Ciantar, Saara Marttila, Sonja Rajić, Daria Kostiniuk, Pashupati P Mishra, Leo-Pekka Lyytikäinen, Nina Mononen, Marcus E Kleber, Winfried März, Mika Kähönen, Olli Raitakari, Terho Lehtimäki, Emma Raitoharju","doi":"10.1080/15592294.2024.2397297","DOIUrl":"10.1080/15592294.2024.2397297","url":null,"abstract":"<p><p>Eastern and Western Finns show a striking difference in coronary heart disease-related mortality; genetics is a known contributor for this discrepancy. Here, we discuss the potential role of DNA methylation in mediating the discrepancy in cardiometabolic disease-risk phenotypes between the sub-populations. We used data from the Young Finns Study (<i>n</i> = 969) to compare the genome-wide DNA methylation levels of East- and West-originating Finns. We identified 21 differentially methylated loci (FDR < 0.05; Δβ >2.5%) and 7 regions (smoothed FDR < 0.05; CpGs ≥ 5). Methylation at all loci and regions associates with genetic variants (<i>p</i> < 5 × 10<sup>-8</sup>). Independently of genetics, methylation at 11 loci and 4 regions associates with transcript expression, including genes encoding zinc finger proteins. Similarly, methylation at 5 loci and 4 regions associates with cardiometabolic disease-risk phenotypes including triglycerides, glucose, cholesterol, as well as insulin treatment. This analysis was also performed in LURIC (<i>n</i> = 2371), a German cardiovascular patient cohort, and results replicated for the association of methylation at cg26740318 and DMR_11p15 with diabetes-related phenotypes and methylation at DMR_22q13 with triglyceride levels. Our results indicate that DNA methylation differences between East and West Finns may have a functional role in mediating the cardiometabolic disease discrepancy between the sub-populations.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2397297"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105578","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-01-21DOI: 10.1080/15592294.2024.2305081
Renan da Silva Santos, Daniel Pascoalino Pinheiro, Carlos Gustavo Hirth, Maria Júlia Barbosa Bezerra, Isabelle Joyce de Lima Silva-Fernandes, Francisca Andréa da Silva Oliveira, Maisa Viana de Holanda Barros, Ester Silveira Ramos, Arlindo A Moura, Odorico de Moraes Manoel Filho, Claudia Pessoa, Cristiana Libardi Miranda Furtado
{"title":"Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection.","authors":"Renan da Silva Santos, Daniel Pascoalino Pinheiro, Carlos Gustavo Hirth, Maria Júlia Barbosa Bezerra, Isabelle Joyce de Lima Silva-Fernandes, Francisca Andréa da Silva Oliveira, Maisa Viana de Holanda Barros, Ester Silveira Ramos, Arlindo A Moura, Odorico de Moraes Manoel Filho, Claudia Pessoa, Cristiana Libardi Miranda Furtado","doi":"10.1080/15592294.2024.2305081","DOIUrl":"10.1080/15592294.2024.2305081","url":null,"abstract":"<p><p>Penile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early events of tumorigenesis and may be involved in the pathogenesis of penile SCC. We sought to evaluate the DNA methylation pattern at H19DMR and its association with HPV infection in men with penile SCC by bisulfite sequencing (bis-seq). We observed an average methylation of 32.2% ± 11.6% at the H19DMR of penile SCC and did not observe an association between the p16<sup>INK4a</sup>+ (<i>p</i> = 0.59) and high-risk HPV+ (<i>p</i> = 0.338) markers with methylation level. The average methylation did not change according to HPV positive for p16<sup>INK4a</sup>+ or hrHPV+ (35.4% ± 10%) and negative for both markers (32.4% ± 10.1%) groups. As the region analysed has a binding site for the CTCF protein, the hypomethylation at the surrounding CpG sites might alter its insulator function. In addition, there was a positive correlation between intense polymorphonuclear cell infiltration and hypomethylation at H19DMR (<i>p</i> = 0.035). Here, we report that hypomethylation at H19DMR in penile SCC might contribute to tumour progression and aggressiveness regardless of HPV infection.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2305081"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512190","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}
EpigeneticsPub Date : 2024-12-01Epub Date: 2024-05-31DOI: 10.1080/15592294.2024.2360160
Drew R Nannini, Rene Cortese, Christopher VonTungeln, Gerhard C Hildebrandt
{"title":"Chemotherapy-induced acceleration of DNA methylation-based biological age in breast cancer.","authors":"Drew R Nannini, Rene Cortese, Christopher VonTungeln, Gerhard C Hildebrandt","doi":"10.1080/15592294.2024.2360160","DOIUrl":"10.1080/15592294.2024.2360160","url":null,"abstract":"<p><p>Breast cancer is the most common cancer diagnosed in women and is often treated with chemotherapy. Although previous studies have demonstrated increasing biological age in patients who receive chemotherapy, evaluation of this association with DNA methylation-based markers of biological ageing may provide novel insight into the role of chemotherapy on the ageing process. We therefore sought to investigate the association between chemotherapy and markers of biological ageing as estimated from DNA methylation in women with breast cancer. DNA methylation profiling was performed on peripheral blood collected from 18 patients before and after the first cycle of chemotherapy using the Infinium HumanMethylation450 BeadChip. Six markers of biological age acceleration were estimated from DNA methylation levels. Multiple linear regression analyses were performed to evaluate the association between each metric of biological age acceleration and chemotherapy. After adjusting for chronological age and race, intrinsic epigenetic age acceleration (<i>p</i> = 0.041), extrinsic epigenetic age acceleration (<i>p</i> = 0.050), PhenoAge acceleration (<i>p</i> = 0.001), GrimAge acceleration (<i>p</i> < 0.001), and DunedinPACE (<i>p</i> = 0.006) were significantly higher and telomere length (<i>p</i> = 0.027) was significantly lower following the first cycle of chemotherapy compared to before treatment initiation. These results demonstrate greater biological ageing as estimated from DNA methylation following chemotherapy in women with breast cancer. Our findings illustrate that cytotoxic therapies may modulate the ageing process among breast cancer patients and may also have implications for age-related health conditions in cancer survivors.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2360160"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183295","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}