[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-326978-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-326978-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","tumor-circadian-clock-strength-influences-metastatic-potential-and-predicts-patient-prognosis-in-luminal-a-breast-cancer","Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer","","Circadian rhythms in human breast tissues and their clinical relevance remain largely undefined. This study reconstructs time-stamped circadian rhythms by integrating locally collected biopsies with public datasets, revealing circadian modulation of inflammatory, EMT, and estrogen responsiveness pathways in noncancerous tissue. In luminal A tumors, clock organization changes and CYCLOPS global rhythm strength varies widely; high-magnitude tumors show elevated EMT cycling and reduced 5-year survival. Molecular clock disruption also reduces invasion in 3D luminal A cultures, linking subtype-specific circadian disruption to metastasis and prognosis.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/tumor-circadian-clock-strength-influences-metastatic-potential-and-predicts-patient-prognosis-in-luminal-a-breast-cancer/326978/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/tumor-circadian-clock-strength-influences-metastatic-potential-and-predicts-patient-prognosis-in-luminal-a-breast-cancer/326978.png","ImageObject",300,407,{"name":42,"@type":43},"Patrick","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is CYCLOPS and why was it used in this study?","Question",{"text":63,"@type":64},"CYCLOPS (Cyclic Ordering by Periodic Structure) is a machine learning approach used to integrate and order transcriptomic data along circadian time across hundreds of patients, addressing the lack of feasible repeated time-course biopsies.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do circadian rhythms differ between noncancerous and luminal A tumor tissues?",{"text":68,"@type":64},"In noncancerous breast tissue, inflammatory, EMT, and estrogen responsiveness pathways show circadian modulation. In luminal A tumors, clock correlation and CYCLOPS magnitude reveal subtype-specific changes and reprogrammed, dampened rhythms.",{"name":70,"@type":61,"acceptedAnswer":71},"What relationship did the study find between circadian rhythm strength and patient outcomes?",{"text":72,"@type":64},"Patients with high-magnitude luminal A tumors, as measured by global rhythm strength, had reduced 5-year survival. Those tumors also showed increased cycling of EMT pathway genes.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},326978,1790189380,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":55,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":113,"preview_page_count":4},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","RESEARCH ARTICLE  \nCELL BIOLOGY  \n OPEN ACCESS  \nTumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer  \nShi-Yang Lia,1, Jan A. Hammarlundb,1, Gang Wuc,d,1, Jia-Wen Liana , Sacha J. Howelle , Robert B. Clarkee, Antony D. Adamsona , Cátia F. Gonçalvesa , John B. Hogeneschc,d , Ron C. Anafif,2,3, and Qing-Jun Menga,2,3  \nEdited by Joseph Takahashi, The University of Texas Southwestern Medical Center, Dallas, TX; received July 14, 2023; accepted December 18, 2023  \nStudies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular circadian rhythms in noncancerous and cancerous human breast tissues and their clinical relevance are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For noncancerous breast tissue, inflammatory, epithelial–mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. LuminalA organoids and informatic ordering of luminalA samples exhibit continued, albeit dampened and reprogrammed rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude luminal A tumors. Surprisingly, patients with high-magnitude tumors had reduced 5-y survival. Correspondingly, 3D luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.  \nbreast cancer | circadian data ordering | circadian medicine | metastasis | prognosis  \nWorldwide, breast cancer is the most common cancer among women (1–3). Over the last decades, the introduction of early detection programs, combined with improvements in systemic therapies, has reduced breast cancer mortality (2–4). Yet, resistance and subsequent relapse remain major issues (3). Women lose more disability-adjusted life years to breast cancer than to any other cancer (5). Adverse effects frequently compromise quality of life (3, 6–8). There remains a clear need to improve the therapeutic index for breast cancer treatments.  \nRecent research has highlighted the critical role of cell-intrinsic circadian rhythms in disease (including cancer) and medicine (9–12). The circadian (~24-hourly) clock is evolutionarily ancient and highly conserved, permitting cells to anticipate daily environmental changes through temporally coordinated metabolic and gene expression profiles (13–15) . A series of transcription-translational feedback loops form the molecular circadian clock (13–16). The positive arm of the central loop includes the transcriptional activators CLOCK and BMAL1 (13–16). The negative arm, which includes the Cryptochrome ( CRY1/CRY2) and Period (PER1/PER2/PER3) genes, later represses translation (13–16) .  \nEpidemiological and animal studies suggest that night shift work that disrupts circadian rhythms increases the risk of developing breast and other cancers, prompting the WHO to classify night shift work as a probable carcinogen (17–19) . Acting in part through an immunosuppressive shift in the tumor environment, chronic circadian disruption increases mammary cancer cell dissemination and metastasis in a mouse model of tumorigenesis (20) .  \nBeyond this basic biology, the molecular circadian clock regulates thousands of genes in a cell and tissue-specific manner. About half of top 100 best-selling drugs in the United States target the product of a circadian gene in mouse tissues (16) . Decades of clinical experience show that time of day can influence chemotherapeutic activity (21, 22). However, the widespread translation of circadian biology in oncology remains slow and serendipitous (23) . Mechanistic knowledge ","cbCairEMizjesm4V","https://ap.wps.com/l/cbCairEMizjesm4V","pdf",10264834,"English","# Introduction\n## Background on circadian disruption and breast cancer\n# Methods\n## Hybrid design and machine learning ordering with CYCLOPS\n# Results\n## Circadian modulation in noncancerous tissue\n## Subtype-specific changes in tumors and luminal A organoids\n## EMT cycling, invasion, and survival associations\n# Significance\n## Implications for patient prognosis and circadian therapy personalization","[{\"question\":\"What is CYCLOPS and why was it used in this study?\",\"answer\":\"CYCLOPS (Cyclic Ordering by Periodic Structure) is a machine learning approach used to integrate and order transcriptomic data along circadian time across hundreds of patients, addressing the lack of feasible repeated time-course biopsies.\"},{\"question\":\"How do circadian rhythms differ between noncancerous and luminal A tumor tissues?\",\"answer\":\"In noncancerous breast tissue, inflammatory, EMT, and estrogen responsiveness pathways show circadian modulation. In luminal A tumors, clock correlation and CYCLOPS magnitude reveal subtype-specific changes and reprogrammed, dampened rhythms.\"},{\"question\":\"What relationship did the study find between circadian rhythm strength and patient outcomes?\",\"answer\":\"Patients with high-magnitude luminal A tumors, as measured by global rhythm strength, had reduced 5-year survival. Those tumors also showed increased cycling of EMT pathway genes.\"}]","Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in luminal A breast cancer | PDF",1789975899]