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This study examines pectoralis major biopsies from individuals with non-metastatic breast cancer and non-cancer controls using single-fiber morphometry and spatial transcriptomics. Fiber-type-specific remodeling shows selective oxidative (type I and IIa) atrophy with relative preservation of glycolytic IIx fibers. Spatial profiling identifies suppressed oxidative programs, mitochondrial dysfunction, and localized catabolic signaling from intramuscular adipocytes, supporting muscle metabolic targeting as a fatigue therapy strategy.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/single-fiber-morphometry-and-spatial-transcriptomics-reveal-selective-oxidative-muscle-fiber-atrophy-in-non-metastatic-breast-cancer/353028/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/single-fiber-morphometry-and-spatial-transcriptomics-reveal-selective-oxidative-muscle-fiber-atrophy-in-non-metastatic-breast-cancer/353028.png","ImageObject",300,407,{"name":92,"@type":93},"eBook King","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-22",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"Why is cancer-related fatigue a focus in non-metastatic breast cancer?","Question",{"text":111,"@type":112},"Fatigue is among the most common and persistent sequelae in breast cancer, including cases where it arises during early-stage disease without cachexia. The study highlights that no approved therapies exist and that underlying mechanisms in skeletal muscle pathology remain insufficiently defined.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"What methods were used to analyze skeletal muscle in this study?",{"text":116,"@type":112},"The research used single-fiber morphometry and spatial transcriptomics on pectoralis major muscle biopsies from people with non-metastatic breast cancer and non-cancer controls.",{"name":118,"@type":109,"acceptedAnswer":119},"Which muscle fiber types showed the most selective changes?",{"text":120,"@type":112},"Single-fiber morphometry revealed selective atrophy of oxidative type I and type IIa fibers, while glycolytic type IIx fibers were relatively preserved.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},353028,1790119774,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},962088006270,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","medRxiv preprint doi: [https://doi.org/10.64898/2026.05.11.26351978](https://doi.org/10.64898/2026.05.11.26351978); this version posted May 20, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nIt is made available under a CC-BY-ND 4.0 International license .  \nTitle:  \nSingle-fiber morphometry and spatial transcriptomics reveal selective oxidative muscle fiber  \natrophy in non-metastatic breast cancer  \nAuthors:  \nAlan D. Mizener1,2 , Stuart A. Clayton3 , Alexa L. Bostic2 , Isabelle A. Oberhauser3 , Hannah E. Wilson4 , Marcella A. Whetsell3 , Hannah Hazard-Jenkins2 , Jessica F. Partin2 , Emidio E. Pistilli2,3*  \nAffiliations:  \n1 – MD/PhD Program, West Virginia University School of Medicine, Morgantown, WV, USA  \n2 – WVU Cancer Institute, West Virginia University School of Medicine, Morgantown, WV, USA  \n3 – Department of Human Performance, Division of Exercise Physiology, West Virginia  \nUniversity School of Medicine, Morgantown, WV, USA  \n4 – Department of Neurosurgery, University of Minnesota School of Medicine, Minneapolis, MN,  \nUSA  \nNOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.  \nmedRxiv preprint doi: [https://doi.org/10.64898/2026.05.11.26351978](https://doi.org/10.64898/2026.05.11.26351978); this version posted May 20, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nIt is made available under a CC-BY-ND 4.0 International license .  \nAbstract:  \nCancer-related fatigue is the most common and persistent symptom in breast cancer, with fatigue reported up to 10 years post-diagnosis. Unlike many cancers, fatigue in breast cancer often arises during early-stage disease in the absence of cachexia. While many factors contribute to fatigue, the direct contribution of cancer-associated skeletal muscle pathology remains poorly understood. Here we analyzed pectoralis major muscle biopsies from individuals with non-metastatic breast cancer and non-cancer controls using single-fiber morphometry and spatial transcriptomics. We identified fiber-type-specific structural alterations and spatially localized transcriptional reprogramming within the muscle microenvironment. Single-fiber morphometry revealed selective atrophy of oxidative type I and type IIa muscle fibers, while glycolytic type IIx fibers were relatively preserved. Concordant spatial transcriptomic profiling revealed suppression of oxidative metabolic programs, evidence of mitochondrial dysfunction, and spatially localized catabolic signaling originating from intramuscular adipocytes. This study introduces an integrated framework for profiling skeletal muscle architecture and spatially localized gene expression in surgically obtained muscle biopsies and represents the first application of spatial transcriptomics to human skeletal muscle from individuals with cancer. These findings demonstrate structural and metabolic remodeling of skeletal muscle in non-metastatic breast cancer and suggest targeting muscle metabolism represents a promising therapeutic strategy for cancer-related fatigue.  \nmedRxiv preprint doi: [https://doi.org/10.64898/2026.05.11.26351978](https://doi.org/10.64898/2026.05.11.26351978); this version posted May 20, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nIt is made available under a CC-BY-ND 4.0 International license .  \nIntroduction:  \nAs breast cancer survival improves, long-term symptom burden has emerged as a defining survivorship challenge, with fatigue being among the most prevalent and persistent sequelae. A meta-analysis of 27 studies involving more than 12,0","cbCaihic2K2j9sn0","https://ap.wps.com/l/cbCaihic2K2j9sn0","pdf",6847276,58,"English","# Abstract\n# Introduction","[{\"question\":\"Why is cancer-related fatigue a focus in non-metastatic breast cancer?\",\"answer\":\"Fatigue is among the most common and persistent sequelae in breast cancer, including cases where it arises during early-stage disease without cachexia. The study highlights that no approved therapies exist and that underlying mechanisms in skeletal muscle pathology remain insufficiently defined.\"},{\"question\":\"What methods were used to analyze skeletal muscle in this study?\",\"answer\":\"The research used single-fiber morphometry and spatial transcriptomics on pectoralis major muscle biopsies from people with non-metastatic breast cancer and non-cancer controls.\"},{\"question\":\"Which muscle fiber types showed the most selective changes?\",\"answer\":\"Single-fiber morphometry revealed selective atrophy of oxidative type I and type IIa fibers, while glycolytic type IIx fibers were relatively preserved.\"}]","Single-fiber morphometry and spatial transcriptomics reveal selective oxidative muscle fiber atrophy in non-metastatic breast cancer | PDF",1790102644,146]