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One subtype showed marked, subtype-specific high expression of MUC12, PIGR, PLA2G2A, SLC4A4, and ZG16 and correlated with favorable outcomes in discovery and independent test cohorts. The remaining four subtypes featured high DEFA6, BST2, MAGEA6, or IGF2, and subtype co-expressed genes also linked to prognosis. A five-signature General Colorectal Cancer Signature (GCS) produced practical individualized predictions and was validated in a xenograft model with distinct metastasis phenotypes. Associations with RAS/RAF and SMAD4/IGF2 were observed without significant effects on survival.",{"@graph":69,"@context":122},[70,84,105],{"@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/comprehensive-colorectal-cancer-stem-cell-transcriptomic-signatures-that-can-predict-patient-prognostic-outcomes-original-article/448107/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/comprehensive-colorectal-cancer-stem-cell-transcriptomic-signatures-that-can-predict-patient-prognostic-outcomes-original-article/448107.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-04","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How were the five CRC-SC transcriptomic subtypes identified?","Question",{"text":112,"@type":113},"mRNA expression profiles from 57 patient-derived CRC-SC lines were compared with normal colonic epithelial stem-like cells (NCE-SCs), and the analysis identified five CRC subtypes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is the General Colorectal Cancer Signature (GCS) and how is it used?",{"text":117,"@type":113},"GCS integrates the five subtype-specific signatures to generate a practical prognostic indicator and individualized predictive signatures for each patient.",{"name":119,"@type":110,"acceptedAnswer":120},"How was the prognostic value of GCS validated?",{"text":121,"@type":113},"Clinical significance was validated using a novel orthotopic xenograft mouse model that recapitulated patient outcomes, including liver and lung metastasis differences by GCS scores.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},448107,1791133490,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","Cancer Science  \nORIGINAL ARTICLE  OPEN ACCESS   \nComprehensive Colorectal Cancer Stem Cell Transcriptomic Signatures That Can Predict Patient Prognostic Outcomes  \nFumihiko Kakizaki1 | Hiroyuki Miyoshi1 | Takehito Yamamoto2,3  | Tomonori Morimoto2  | Hiroyuki Matsubara2 | Shoichi Kitano1,2  | Tadayoshi Yamaura2 | Hisatsugu Maekawa1,2 | J. B. Brown4 | Tosiya Shun Sato5 | Kazutaka Obama2 | Yoshiharu Sakai2 | Kenji Kawada2 | Makoto Mark Taketo1,3   \n1Personalized Cancer Therapy Laboratory, Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan | 2Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan | 3Medical Research Institute Kitano Hospital, Osaka, Japan | 4Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan | 5Innovation Research Promotion Center, Institute of  \nStatistical Mathematics, and Data Science and AI, Shiga University, Hikone, Shiga, Japan Correspondence: Makoto Mark Taketo ([taketo@mfour.med.kyoto-u.ac.jp](taketo@mfour.med.kyoto-u.ac.jp))  \nReceived: 22 May 2025 | Revised: 13 October 2025 | Accepted: 17 October 2025  \nFunding: This work was supported by Grants-in-Aid for Scientific Research (JP18H02639 and JP21K06948) from the Japan Society for the Promotion of Science (H.M. and F.K., respectively), the Program for Creating STart-ups from Advanced Research and Technology (ST261001TT) from the Japan Science and Technology Agency (M.M.T.), the Practical Research for Innovative Cancer Control (ck0106195h) from the Japan Agency for Medical Research and Development (M.M.T.), the Kyoto University Venture Incubation from the Kyoto University Office of Society-Academia Collaboration for Innovation (M.M.T.), and Support from the Institute for Advancement of Clinical and Translational Science (iACT), KUHP (M.M.T.) .  \nKeywords: colorectal neoplasms | metastasis | neoplastic stem cells | prognosis | transcriptome  \nABSTRACT  \nBased on mRNA Expression Profiles of 57 Patient-Derived Colorectal Cancer Stem-Like Cell (CRC-SC) Lines Compared With Normal Colonic Epithelial Stem-Like Cells (NCE-SCs), we Identified Five CRC Subtypes. The First Subtype ofCRC-SCs Showed Markedly Increased Expression of MUC12, PIGR, PLA2G2A, SLC4A4, and ZG16, Which Were Barely Detectable in the Other Subtypes. Importantly, Their Expression Correlated With Favorable Outcomes in Both the Discovery Cohort and Independent Two Test Cohorts From Public Databases. The Remaining Four Subtypes Showed High Expression of DEFA6, BST2, MAGEA6, or IGF2 Compared With NCE-SCs. Although the Expression of Each Gene Individually Influenced Patient Outcomes, Additional Co-Expressed Genes Within Each Subtype Were Also Associated With Prognosis. Furthermore, Integrating the Five SubtypeSpecific Signatures Produced a Practical Prognostic Indicator, Designated as the General Colorectal Cancer Signature (GCS), and Provided Individualized Predictive Signatures for Each Patient. The Clinical Significance of GCS Was Further Validated ina Novel Orthotopic Xenograft Mouse Model, Which Recapitulated Patient Outcomes: CRC-SCs With Low GCS Scores Developed Distinct Liver and Lung Metastases, Whereas Those With High Scores Did Not. Apparent Associations Were Observed Between Activating RAS/RAF Mutations and BST2 Expression, and Between the Absence of SMAD4 Mutation and IGF2 Expression, but These Had no Significant Impact on Patient Survival, Suggesting That Driver Gene Mutations May Not Directly Influence GCS. Collectively, Our Findings Provide a Comprehensive Overview of Clinically Relevant Molecular Subtypes of CRC-SCs, Representing the Current Landscape of CRC Molecular Expression Subtypes. They Also Enable Rapid, Low-Cost Outcome Prediction and Suggest Potential Targets for Therapeutics Development.  \n\n| Abbreviations: CI, confidence interval; CM, conditioned medium; CMS, consensus molecular subtype; CRC, colorectal cancer; CRIS, CRC intrinsic subtype; DFS, disea","cbCaifix8i5BaIad","https://ap.wps.com/l/cbCaifix8i5BaIad","pdf",4497757,15,"English","# Abstract\n# Introduction","[{\"question\":\"How were the five CRC-SC transcriptomic subtypes identified?\",\"answer\":\"mRNA expression profiles from 57 patient-derived CRC-SC lines were compared with normal colonic epithelial stem-like cells (NCE-SCs), and the analysis identified five CRC subtypes.\"},{\"question\":\"What is the General Colorectal Cancer Signature (GCS) and how is it used?\",\"answer\":\"GCS integrates the five subtype-specific signatures to generate a practical prognostic indicator and individualized predictive signatures for each patient.\"},{\"question\":\"How was the prognostic value of GCS validated?\",\"answer\":\"Clinical significance was validated using a novel orthotopic xenograft mouse model that recapitulated patient outcomes, including liver and lung metastasis differences by GCS scores.\"}]","Comprehensive Colorectal Cancer Stem Cell Transcriptomic Signatures That Can Predict Patient Prognostic Outcomes - Original Article | PDF",1790725374,38]