[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-detail-462668-en":59,"doc-seo-462668-105":82},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":5,"data":60},{"doc_id":61,"user_id":62,"nickname":63,"user_avatar":64,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":66,"doc_content":67,"file_id":68,"file_url":69,"file_type":70,"file_size":71,"view_count":72,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":73,"language":74,"language_code":75,"site_id":76,"html_lang":75,"table_of_contents":77,"faqs":78,"seo_title":79,"seo_description":66,"update_tm":80,"read_time":81,"preview_page_count":4},462668,1374404737137,"Adam","https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Subtype-Specific m6A circRNA Methylation Patterns Identify Epigenetic Biomarker Candidates of Potential Diagnostic and Prognostic Significance in Breast Cancer","Breast cancer subtypes show distinct pathobiological and clinical behaviors, and triple-negative breast cancer remains highly aggressive and treatment resistant due to absent hormone and HER2 targets. This study maps m6A-modified circRNA methylation patterns across TNBC and luminal breast tumors, using methylated RNA immunoprecipitation with microarray profiling, followed by integrated differential analysis. Subtype-specific circRNA m6A signatures were linked to biological pathways and survival outcomes, with selected circRNAs displaying diagnostic performance (AUC > 0.80). Findings support circRNA candidates for biomarker-driven subtype classification and prognosis in breast cancer, with implications for epigenetic and post-transcriptional therapeutic strategies.","Article  \nSubtype-Specific m6 A circRNA Methylation Patterns Identify Epigenetic Biomarker Candidates of Potential Diagnostic and Prognostic Significance in Breast Cancer  \nAmal Qattan 1,2, *, Wafa Alkhayal 3, Kausar Suleman 4, Taher Al-Tweigeri 4 and Asma Tulbah 5  \nAcademic Editor: Zhongzhou Chen  \nReceived: 11 November 2025  \nRevised: 10 December 2025  \nAccepted: 21 December 2025  \nPublished: 4 January 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Innovation and Research Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia  \n2 College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia  \n3 Surgical Oncology Department, Cancer Centre of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia; [wkhayal@kfshrc.edu.sa](wkhayal@kfshrc.edu.sa)  \n4 Medical Oncology Department, Cancer Centre of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia; [ksuleman@kfshrc.edu.sa](ksuleman@kfshrc.edu.sa) (K.S.); [ttwegieri@kfshrc.edu.sa](ttwegieri@kfshrc.edu.sa) (T.A.-T.)  \n5 Pathology and Laboratory Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia; [tulbah@kfshrc.edu.sa](tulbah@kfshrc.edu.sa)  \n* Correspondence: [akattan@kfshrc.edu.sa](akattan@kfshrc.edu.sa)  \nAbstract  \nBreast cancer subtypes are known to have important pathobiological and clinical features. For example, triple-negative breast cancer (TNBC) remains one of the most aggressive and treatment-resistant breast cancer subtypes, lacking hormone and HER2 targets. Increasing evidence suggests that circular RNAs (circRNAs) and their N6-methyladenosine (m6A) modifications play critical roles in cancer biology through the regulation of gene expression, stability, and signaling networks. This study aimed to identify m6A methylation patterns in circRNAs among breast cancer subtypes, explore their potential biological functions, and assess their diagnostic and prognostic relevance compared with luminal breast cancer subtypes. Genome-wide profiling of m6A-modified circRNAs was conducted in TNBC and luminal breast tumor samples using methylated RNA immunoprecipitation followed by microarray analysis. Differential methylation and expression analyses were integrated with pathway enrichment, survival correlation, and receiver operating characteristic (ROC) curve assessments to identify subtype-specific and clinically relevant circRNA candidates. Distinct m6A circRNA methylation signatures were identified across breast cancer subtypes, with TNBC showing enrichment in pathways related to Wnt/β-catenin, CDC42 GTPase signaling, and cytoskeletal remodeling. Several circRNAs, including those derived from ZBTB16, DOCK1, METTL8, and VAV3, exhibited significant hypermethylation and high diagnostic accuracy (AUC > 0.80) . Survival analyses revealed associations between circRNAs from key host genes and overall or relapse-free survival, suggesting prognostic potential. These findings uncover subtype-specific m6A circRNA methylation landscapes that may contribute to tumor aggressiveness and heterogeneity. Identified circRNAs represent candidates for investigation as biomarkers for subtype classification and prognosis and may inform future research into epigenetic and post-transcriptional therapeutic targets in breast cancer.  \nKeywords: triple-negative breast cancer; non-coding RNA; circRNA; microRNA; m6Amethylation; epitranscriptomics; post-transcriptional regulation; biomarker; therapeutic target; precision oncology; targeted therapy; tumor progression  \n1. Introduction  \nBreast cancer subtypes are defined according to gene expression profiles and are routinely classified by immunohistochemistry in clinical practice [1] . Such classification has important implicati","cbCaipgxThVKSNvw","https://ap.wps.com/l/cbCaipgxThVKSNvw","pdf",17978937,11,29,"English","en",105,"# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What was the study’s main goal regarding breast cancer subtypes?\",\"answer\":\"To identify m6A methylation patterns in circRNAs among breast cancer subtypes, examine potential biological functions, and evaluate diagnostic and prognostic relevance compared with luminal subtypes.\"},{\"question\":\"How were m6A-modified circRNAs profiled in TNBC and luminal tumors?\",\"answer\":\"The study used methylated RNA immunoprecipitation followed by microarray analysis, then integrated differential methylation and expression analyses with pathway enrichment and survival/ROC assessments.\"},{\"question\":\"Which results indicate potential diagnostic and prognostic value?\",\"answer\":\"Subtype-specific m6A circRNA methylation signatures were found, and several circRNAs showed hypermethylation with high diagnostic accuracy (AUC \\u003e 0.80). Survival analyses also revealed associations with overall or relapse-free survival.\"}]","Subtype-Specific m6A circRNA Methylation Patterns Identify Epigenetic Biomarker Candidates of Potential Diagnostic and Prognostic Significance in Breast Cancer | PDF",1790764836,73,{"code":4,"msg":83,"data":84},"ok",{"site_id":76,"language":75,"slug":85,"title":65,"keywords":86,"description":66,"schema_data":87,"social_meta":141,"head_meta":143,"extra_data":145,"updated_unix":146},"subtype-specific-m6a-circrna-methylation-patterns-identify-epigenetic-biomarker-candidates-of-potential-diagnostic-and-prognostic-significance-in-breast-cancer","",{"@graph":88,"@context":140},[89,103,123],{"@type":90,"itemListElement":91},"BreadcrumbList",[92,96,98,101],{"item":93,"name":94,"@type":95,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":97,"name":9,"@type":95,"position":14},"https://docshare.wps.com/document/",{"item":99,"name":35,"@type":95,"position":100},"https://docshare.wps.com/document/healthcare/",3,{"item":102,"name":65,"@type":95,"position":19},"https://docshare.wps.com/document/subtype-specific-m6a-circrna-methylation-patterns-identify-epigenetic-biomarker-candidates-of-potential-diagnostic-and-prognostic-significance-in-breast-cancer/462668/",{"url":102,"name":65,"@type":104,"image":105,"author":110,"headline":65,"publisher":112,"fileFormat":115,"inLanguage":75,"description":66,"dateModified":116,"datePublished":117,"encodingFormat":115,"isAccessibleForFree":118,"interactionStatistic":119},"DigitalDocument",{"url":106,"@type":107,"width":108,"height":109},"https://docshare.wps.com/thumbnails/subtype-specific-m6a-circrna-methylation-patterns-identify-epigenetic-biomarker-candidates-of-potential-diagnostic-and-prognostic-significance-in-breast-cancer/462668.png","ImageObject",300,407,{"name":63,"@type":111},"Person",{"url":93,"name":113,"@type":114},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":120,"interactionType":121,"userInteractionCount":72},"InteractionCounter",{"@type":122},"ViewAction",{"@type":124,"mainEntity":125},"FAQPage",[126,132,136],{"name":127,"@type":128,"acceptedAnswer":129},"What was the study’s main goal regarding breast cancer subtypes?","Question",{"text":130,"@type":131},"To identify m6A methylation patterns in circRNAs among breast cancer subtypes, examine potential biological functions, and evaluate diagnostic and prognostic relevance compared with luminal subtypes.","Answer",{"name":133,"@type":128,"acceptedAnswer":134},"How were m6A-modified circRNAs profiled in TNBC and luminal tumors?",{"text":135,"@type":131},"The study used methylated RNA immunoprecipitation followed by microarray analysis, then integrated differential methylation and expression analyses with pathway enrichment and survival/ROC assessments.",{"name":137,"@type":128,"acceptedAnswer":138},"Which results indicate potential diagnostic and prognostic value?",{"text":139,"@type":131},"Subtype-specific m6A circRNA methylation signatures were found, and several circRNAs showed hypermethylation with high diagnostic accuracy (AUC > 0.80). Survival analyses also revealed associations with overall or relapse-free survival.","https://schema.org",{"og:url":102,"og:type":142,"og:title":65,"og:site_name":113,"og:description":66},"article",{"robots":144,"canonical":102},"index,follow",{"doc_id":61,"site_id":76},1791001010]