Epigenetics最新文献

{"title":"Stress-induced epigenetic effects driven by maternal lactation in dairy cattle: a comethylation network approach.","authors":"Adrián López-Catalina, Antonio Reverter, Pamela A Alexandre, Loan T Nguyen, Oscar González-Recio","doi":"10.1080/15592294.2024.2381856","DOIUrl":"10.1080/15592294.2024.2381856","url":null,"abstract":"<p><p>Epigenetic marks do not follow the Mendelian laws of inheritance. The environment can alter the epigenotype of an individual when exposed to different external stressors. In lactating cows, the first stages of gestation overlap with the lactation peak, creating a negative energy balance that is difficult to overcome with diet. This negative energy balance could affect early embryo development that must compete with the mammary tissue for nutrients. We hypothesize that the methylation profiles of calves born to nonlactating heifers are different from those of calves born to lactating cows. We found 50,277 differentially methylated cytosines and 2,281 differentially methylated regions between these two groups of animals. A comethylation network was constructed to study the correlation between the phenotypes of the mothers and the epigenome of the calves, revealing 265 regions associated with the phenotypes. Our study revealed the presence of DMCs and DMRs in calves gestated by heifers and lactating cows, which were linked to the dam's lactation and the calves' ICAP and milk EBV. Gene-specific analysis highlighted associations with vasculature and organ morphogenesis and cell communication and signalling. These finding support the hypothesis that calves gestated by nonlactating mothers have a different methylation profile than those gestated by lactating cows.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751406","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":"LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea.","authors":"Kai Chen, Baiqing Ou, Quan Huang, Daqing Deng, Yi Xiang, Fang Hu","doi":"10.1080/15592294.2023.2293409","DOIUrl":"10.1080/15592294.2023.2293409","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of NEAT1 in T2DM-OSA and the underlying mechanism. KKAy mice were exposed to intermittent hypoxia (IH) or intermittent normoxia to generate a T2DM-OSA mouse model. HMEC-1 cells were treated with high glucose (HG) and IH to construct a T2DM-OSA cell model. RNA expression was detected by qRT-PCR. The protein expression of Apelin, NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and up-frameshift suppressor 1 (UPF1) was assessed using western blot. Cell injury was evaluated using flow cytometry, enzyme-linked immunosorbent assay, and oxidative stress kit assays. RIP, RNA pull-down, and actinomycin D assays were performed to determine the associations between NEAT1, UPF1, and Apelin. NEAT1 expression was upregulated in the aortic vascular tissues of mice with T2DM exposed to IH and HMEC-1 cells stimulated with HG and IH, whereas Apelin expression was downregulated. The absence of NEAT1 protected HMEC-1 cells from HG- and IH-induced damage. Furthermore, NEAT1 destabilized Apelin mRNA by recruiting UPF1. Apelin overexpression decreased HG- and IH-induced injury to HMEC-1 cells by activating the Nrf2/HO-1 pathway. Moreover, NEAT1 knockdown reduced HG- and IH-induced injury to HMEC-1 cells through Apelin. NEAT1 silencing reduced HMEC-1 cell injury through the Apelin/Nrf2/HO-1 signalling pathway in T2DM-OSA.<b>Abbreviations:</b> LncRNAs, long non-coding RNAs; T2DM, type 2 diabetes mellitus; OSA, obstructive sleep apnoea; NEAT1, nuclear paraspeckle assembly transcript 1; IH, intermittent hypoxia; HMEC-1, human microvascular endothelial cells; HG, high glucose; Nrf2, NF-E2-related factor 2; UPF1, up-frameshift suppressor 1; HO-1, haem oxygenase-1; qRT-PCR, quantitative real-time polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; TNF-α, tumour necrosis factor-α; CCK-8, Cell Counting Kit-8; IL-1β, interleukin-1β; ROS, reactive oxygen species; MDA, malondialdehyde; SOD, superoxide dismutase; RIP, RNA immunoprecipitation; SD, standard deviations; GSH, glutathione; AIS, acute ischaemic stroke; HMGB1, high mobility group box-1 protein; TLR4, toll-like receptor 4.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10795783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485467","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":"MIMOSA: a resource consisting of improved methylome prediction models increases power to identify DNA methylation-phenotype associations.","authors":"Hunter J Melton, Zichen Zhang, Hong-Wen Deng, Lang Wu, Chong Wu","doi":"10.1080/15592294.2024.2370542","DOIUrl":"10.1080/15592294.2024.2370542","url":null,"abstract":"<p><p>Although DNA methylation (DNAm) has been implicated in the pathogenesis of numerous complex diseases, from cancer to cardiovascular disease to autoimmune disease, the exact methylation sites that play key roles in these processes remain elusive. One strategy to identify putative causal CpG sites and enhance disease etiology understanding is to conduct methylome-wide association studies (MWASs), in which predicted DNA methylation that is associated with complex diseases can be identified. However, current MWAS models are primarily trained using the data from single studies, thereby limiting the methylation prediction accuracy and the power of subsequent association studies. Here, we introduce a new resource, MWAS Imputing Methylome Obliging Summary-level mQTLs and Associated LD matrices (MIMOSA), a set of models that substantially improve the prediction accuracy of DNA methylation and subsequent MWAS power through the use of a large summary-level mQTL dataset provided by the Genetics of DNA Methylation Consortium (GoDMC). Through the analyses of GWAS (genome-wide association study) summary statistics for 28 complex traits and diseases, we demonstrate that MIMOSA considerably increases the accuracy of DNA methylation prediction in whole blood, crafts fruitful prediction models for low heritability CpG sites, and determines markedly more CpG site-phenotype associations than preceding methods. Finally, we use MIMOSA to conduct a case study on high cholesterol, pinpointing 146 putatively causal CpG sites.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534029","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":"Direction-aware functional class scoring enrichment analysis of infinium DNA methylation data.","authors":"Mark Ziemann, Mandhri Abeysooriya, Anusuiya Bora, Séverine Lamon, Mary Sravya Kasu, Mitchell W Norris, Yen Ting Wong, Jeffrey M Craig","doi":"10.1080/15592294.2024.2375022","DOIUrl":"10.1080/15592294.2024.2375022","url":null,"abstract":"<p><p>Infinium Methylation BeadChip arrays remain one of the most popular platforms for epigenome-wide association studies, but tools for downstream pathway analysis have their limitations. Functional class scoring (FCS) is a group of pathway enrichment techniques that involve the ranking of genes and evaluation of their collective regulation in biological systems, but the implementations described for Infinium methylation array data do not retain direction information, which is important for mechanistic understanding of genomic regulation. Here, we evaluate several candidate FCS methods that retain directional information. According to simulation results, the best-performing method involves the mean aggregation of probe limma t-statistics by gene followed by a rank-ANOVA enrichment test using the mitch package. This method, which we call 'LAM,' outperformed an existing over-representation analysis method in simulations, and showed higher sensitivity and robustness in an analysis of real lung tumour-normal paired datasets. Using matched RNA-seq data, we examine the relationship of methylation differences at promoters and gene bodies with RNA expression at the level of pathways in lung cancer. To demonstrate the utility of our approach, we apply it to three other contexts where public data were available. First, we examine the differential pathway methylation associated with chronological age. Second, we investigate pathway methylation differences in infants conceived with in vitro fertilization. Lastly, we analyse differential pathway methylation in 19 disease states, identifying hundreds of novel associations. These results show LAM is a powerful method for the detection of differential pathway methylation complementing existing methods. A reproducible vignette is provided to illustrate how to implement this method.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534028","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":"m6A reader YTHDC2 mediates NCOA4 mRNA stability affecting ferritinophagy to alleviate secondary injury after intracerebral haemorrhage.","authors":"Fengfeng Li, Fang Wang, Lei Wang, Jianhua Wang, Shanshan Wei, Junjun Meng, Yanan Li, Lei Feng, Pei Jiang","doi":"10.1080/15592294.2024.2326868","DOIUrl":"10.1080/15592294.2024.2326868","url":null,"abstract":"<p><p>Oxidative stress and neuronal dysfunction caused by intracerebral haemorrhage (ICH) can lead to secondary injury. The m6A modification has been implicated in the progression of ICH. This study aimed to investigate the role of the m6A reader YTHDC2 in ICH-induced secondary injury. ICH models were established in rats using autologous blood injection, and neuronal cell models were induced with Hemin. Experiments were conducted to overexpress YTH domain containing 2 (YTHDC2) and examine its effects on neuronal dysfunction, brain injury, and neuronal ferritinophagy. RIP-qPCR and METTL3 silencing were performed to investigate the regulation of YTHDC2 on nuclear receptor coactivator 4 (NCOA4). Finally, NCOA4 overexpression was used to validate the regulatory mechanism of YTHDC2 in ICH. The study found that YTHDC2 expression was significantly downregulated in the brain tissues of ICH rats. However, YTHDC2 overexpression improved neuronal dysfunction and reduced brain water content and neuronal death after ICH. Additionally, it reduced levels of ROS, NCOA4, PTGS2, and ATG5 in the brain tissues of ICH rats, while increasing levels of FTH and FTL. YTHDC2 overexpression also decreased levels of MDA and Fe2+ in the serum, while promoting GSH synthesis. In neuronal cells, YTHDC2 overexpression alleviated Hemin-induced injury, which was reversed by Erastin. Mechanistically, YTHDC2-mediated m6A modification destabilized NCOA4 mRNA, thereby reducing ferritinophagy and alleviating secondary injury after ICH. However, the effects of YTHDC2 were counteracted by NCOA4 overexpression. Overall, YTHDC2 plays a protective role in ICH-induced secondary injury by regulating NCOA4-mediated ferritinophagy.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093595","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":"PRKCB methylation: a potential biomarker of MDD with childhood chronic stress, a cross-sectional study in drug-naive, first-episode adolescent MDD.","authors":"Yuanmei Tao, Meijiang Jin, Hang Zhang, Maojia Ran, Hanmei Xu, Shoukang Zou, Fang Deng, Lijuan Huang, Hong Zhang, Xiaolan Wang, Yanping Wang, Huijin Hou, Shufang Liang, Xiaohong Ma, Li Yin","doi":"10.1080/15592294.2024.2408159","DOIUrl":"10.1080/15592294.2024.2408159","url":null,"abstract":"<p><p>The purpose of this study was to investigate the relationship between childhood chronic stress(CCS), Protein kinase C beta (PRKCB) methylation and adolescent major depressive disorder (MDD). After recruiting 100 adolescents with MDD and 50 healthy controls (HCs), we evaluated the severity of CCS. PRKCB methylation was assessed by pyrosequencing using whole blood-derived DNA. To explore the relationship between CCS, PRKCB and adolescent MDD, we conducted correlation analysis and regression analysis, and constructed multiplicative interaction models and generalized linear models. PRKCB methylation and CCS were both found to be associated with MDD, and CCS was associated with PRKCB methylation. No significant CCS-PRKCB methylation interactions were observed. However, we found the interaction of CCS and MDD on PRKCB methylation. Our results found that PRKCB methylation was influenced by CCS and the disease itself, and PRKCB methylation was significantly positively associated with MDD severity, suggesting that PRKCB methylation may be a potential biomarker for adolescent MDD. This study is a cross-sectional observational study, which cannot draw the conclusion of causality. Prospective cohort studies are needed to further examine the relationship between CCS, adolescent MDD, and PRKCB methylation.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343918","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":"Detection of DNA methylation from buccal swabs using nanopore sequencing to study stunting.","authors":"Alim El-Hakim, Inswasti Cahyani, Muhammad Zulfikar Arief, Gilang Akbariani, Asep Muhamad Ridwanuloh, Syam Budi Iryanto, Ratih Rahayu, Daeng Deni Mardaeni, Vincentius Budhyanto, Yusnita, Wening Sari, Anggi Pn Hidayati, Intan Razari, Silviatun Nihayah, Kinasih Prayuni, Chandra Utomo, Ratih Asmana Ningrum, Susanti Susanti, Ahmad Utomo","doi":"10.1080/15592294.2024.2418717","DOIUrl":"10.1080/15592294.2024.2418717","url":null,"abstract":"<p><p>Stunting is the result of chronic malnutrition due to the lack of micronutrient-based methyl donors required for epigenetic programming during the first 1000 days of life. Methylation studies using bisulfite conversion from blood DNA are invasive and may not be practical for large-scale epidemiological investigation or nutrition intervention programs. Buccal epithelial methylation may reflect early germline methylation. Therefore, buccal cells can serve as convenient sample sources to collect biomarkers associated with the risk of stunting. This study aims to describe the feasibility of nanopore adaptive sampling in detecting DNA methylation from children's buccal DNA. We used adaptive sampling of Oxford Nanopore Technology on barcoded samples to describe differential methylation associated with malnutrition. Overall, the level of 5-methylcytosine (5mC) was lower in stunted children than in normal children. We also found differentially methylated regions at the MIR6724 and RNA45SN1 gene loci on chromosome 21, which was higher in stunted children than in normal children. We described and detected differential DNA methylation in the locus previously not known to be associated with stunting. Interestingly, this locus on chromosome 21 has been implicated in the stunted phenotype of Down syndrome.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567113","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":"TET1 inhibits the migration and invasion of cervical cancer cells by regulating autophagy.","authors":"Ji Ren, Xiuying Chen, Jing Li, Yuxin Zan, Shan Wang, Yujie Tan, Yan Ding","doi":"10.1080/15592294.2024.2323751","DOIUrl":"10.1080/15592294.2024.2323751","url":null,"abstract":"<p><p>Methylation modifications play pertinent roles in regulating gene expression and various biological processes. The silencing of the demethylase enzyme TET1 can affect the expressions of key oncogenes or tumour suppressor genes, thus contributing to tumour formation. Nonetheless, how TET1 affects the progression of cervical cancer is yet to be elucidated. In this study, we found that the expression of TET1 was significantly downregulated in cervical cancer tissues. Functionally, TET1 knockdown in cervical cancer cells can promote cell proliferation, migration, invasion, cervical xenograft tumour formation and EMT. On the contrary, its overexpression can reverse the aforementioned processes. Moreover, the autophagy level of cervical cancer cells can be enhanced after TET1 knockdown. Mechanistically, methylated DNA immunoprecipitation (MeDIP)-sequencing and MeDIP quantitative real-time PCR revealed that TET1 mediates the methylation of autophagy promoter regions. These findings suggest that TET1 affects the autophagy of cervical cancer cells by altering the methylation levels of NKRF or HIST1H2AK, but the specific mechanism needs to be investigated further.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021233","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":"History of exposure to copper influences transgenerational gene expression responses in <i>Daphnia magna</i>.","authors":"Guilherme Jeremias, Ana-Belén Muñiz-González, Fernando José Mendes Gonçalves, José-Luis Martínez-Guitarte, Jana Asselman, Joana Luísa Pereira","doi":"10.1080/15592294.2023.2296275","DOIUrl":"10.1080/15592294.2023.2296275","url":null,"abstract":"<p><p>The establishment of transgenerational effects following chemical exposure is a powerful phenomenon, capable of modulating ecosystem health beyond exposure periods. This study assessed the transgenerational effects occurring due to copper exposure in the invertebrate <i>D. magna</i> at the transcriptional level, while evaluating the role of exposure history on such responses. Thus, daphnids acclimated for several generations in a copper vs. clean medium were then exposed for one generation (F0) to this metal, and monitored for the following non-exposed generations (F1, F2 and F3). Organisms differing in exposure histories showed remarkably different transcriptional profiles at the F0, with naïve organisms being more profoundly affected. These trends were confirmed for F3 treatments, which presented different transcriptional patterns for genes involved in detoxification, oxidative stress, DNA damage repair, circadian clock functioning and epigenetic regulation. Furthermore, regardless of exposure history, a great number of histone modifier genes were always found transcriptionally altered, thus suggesting the involvement of histone modifications in the response of <i>Daphnia</i> to metal exposure. Lastly, remarkably distinct transgenerational transcriptional responses were found between naïve and non-naïve organisms, thereby highlighting the influence of exposure history on gene expression and confirming the capacity of metals to determine transgenerational transcriptional effects across non-exposed generations.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058236","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":"Evaluating the utility of <i>ZNF331</i> promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance).","authors":"Elizabeth S Nakasone, Tyler J Zemla, Ming Yu, She Yu Lin, Fang-Shu Ou, Kelly Carter, Federico Innocenti, Leonard Saltz, William M Grady, Stacey A Cohen","doi":"10.1080/15592294.2024.2349980","DOIUrl":"10.1080/15592294.2024.2349980","url":null,"abstract":"<p><p>While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of <i>ZNF331</i> promoter hypermethylation (m<i>ZNF331</i>) as a prognostic and predictive marker in colon cancer. We examined the association of m<i>ZNF331</i> with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. <i>ZNF331</i> promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of m<i>ZNF331</i> in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. m<i>ZNF331</i> was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with m<i>ZNF331</i> compared to unmethylated <i>ZNF331</i> (unm<i>ZNFF31</i>). There was no significant difference in disease-free or overall survival between patients with m<i>ZNF331</i> versus unm<i>ZNF331</i> colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by <i>ZNF331</i> methylation status. While <i>ZNF331</i> promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of m<i>ZNF331</i> as a prognostic and predictive marker.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876160","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}