[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332100-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-332100-en":130},{"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","identification-of-unique-rectal-cancer-specific-subtypes","Identification of unique rectal cancer-specific subtypes","","Existing colorectal cancer subtyping approaches do not sufficiently account for expression-profile differences between colon and rectal tissues, and neoadjuvant chemoradiotherapy may substantially alter gene expression in rectal tumors. Using rectal and colon mRNA profiles from 2121 samples, the study shows that CMS differs in treatment-naïve rectal versus colon cancers and shifts after neoadjuvant CRT. Clustering 182 untreated rectal cancers identified three robust RSS and enables more accurate prognosis prediction than CMS.",{"@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/identification-of-unique-rectal-cancer-specific-subtypes/332100/",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/identification-of-unique-rectal-cancer-specific-subtypes/332100.png","ImageObject",300,407,{"name":42,"@type":43},"Ivy","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-07","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are colon and rectal cancer subtyping methods not directly interchangeable?","Question",{"text":63,"@type":64},"Existing colorectal subtyping methods were generated without strongly considering expression differences between colon and rectal tissues. The study also notes that neoadjuvant chemoradiotherapy can significantly impact rectal cancer gene expression.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What effect did neoadjuvant chemoradiotherapy have on CMS subtypes in rectal cancers?",{"text":68,"@type":64},"Neoadjuvant chemoradiotherapy exposure produced a strong shift in CMS subtypes in rectal cancers, indicating treatment can change the molecular subtype distribution.",{"name":70,"@type":61,"acceptedAnswer":71},"How many rectal cancer-specific subtypes were identified, and what distinguishes them?",{"text":72,"@type":64},"Three robust RSS were identified. RSS1 has better disease-free survival with high MYC target gene expression and low angiogenesis activity; RSS2 has worse survival with low regulatory T cells, strong EMT/angiogenesis signaling, and high TGF-β, NF-κB, and TNF-α activation; RSS3 shows deactivation of EGFR, MAPK, and WNT pathways.","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},332100,1790012751,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":123,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144,"preview_page_count":4},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","British Journal of Cancer [www.nature.com/bjc](www.nature.com/bjc)  \nARTICLE OPEN   \nGenetics and Genomics  \nIdentification of unique rectal cancer-specific subtypes  \nBatuhan Kisakol1,2, Anna Matveeva1,2, Manuela Salvucci 1,2, Alexander Kel3, Elizabeth McDonough 4, Fiona Ginty4, Daniel B. Longley5 and Jochen H. M. Prehn 1,2 ✉  \n© The Author(s) 2024  \nBACKGROUND: Existing colorectal cancer subtyping methods were generated without much consideration of potential differences in expression profiles between colon and rectal tissues. Moreover, locally advanced rectal cancers at resection often have received neoadjuvant chemoradiotherapy which likely has a significant impact on gene expression.  \nMETHODS: We collected mRNA expression profiles for rectal and colon cancer samples (n = 2121) . We observed that (i) Consensus Molecular Subtyping (CMS) had a different prognosis in treatment-naïve rectal vs. colon cancers, and (ii) that neoadjuvant chemoradiotherapy exposure produced a strong shift in CMS subtypes in rectal cancers. We therefore clustered 182 untreated rectal cancers to find rectal cancer-specific subtypes (RSSs) .  \nRESULTS: We identified three robust subtypes. We observed that RSS1 had better, and RSS2 had worse disease-free survival. RSS1 showed high expression of MYC target genes and low activity of angiogenesis genes. RSS2 exhibited low regulatory T cell abundance, strong EMT and angiogenesis signalling, and high activation of TGF-β, NF-κB, and TNF-α signalling. RSS3 was characterised by the deactivation of EGFR, MAPK and WNT pathways.  \nCONCLUSIONS: We conclude that RSS subtyping allows for more accurate prognosis predictions in rectal cancers than CMS subtyping and provides new insight into targetable disease pathways within these subtypes.  \nBritish Journal of Cancer (2024) 130:1809–1818; [https://doi.org/10.1038/s41416-024-02656-0](https://doi.org/10.1038/s41416-024-02656-0)  \nBACKGROUND  \nColorectal cancer is the third most common cancer worldwide. When considered separately colon cancer is the fourth and rectal cancer is the eighth most common cancer [1] . Rectal and colon cancers exhibit histological and anatomical differences which have been associated with different clinical outcomes [2, 3] . While stage III and high-risk stage II colon cancer patients are treated with adjuvant chemotherapy post-resection [4], locally advanced rectal cancers are routinely treated both in neoadjuvant and adjuvant settings. Neoadjuvant chemoradiotherapy (CRT) is performed in stage 3 and high-risk stage 2 rectal cancers to shrink the tumour and improve the effectiveness of surgical resection [5] .  \nUnsupervised, transcriptome-based molecular subtyping of colorectal cancers has revealed new insights into the heterogeneity of colorectal cancer and the underlying disease biology within subtypes [6]. ‘Consensus molecular subtypes’ (CMS) defined by Guinney et al. [7] were established subsequent to several previous subtyping studies [8–13] and employed Markov clustering on the similarity network of the previously identified clusters to define four CMS. However, colon cancer samples comprised the vast majority (85%) of the study samples [14] . Moreover, rectal cancers at resection may have already been subjected to  \nneoadjuvant CRT, which is likely to induce significant alterationsin gene expression profiles [5] .  \nSystematic and specific subtyping of treatment-naïve rectal cancers has so far not been performed. Therefore, by focusing on untreated rectal cancer samples, we refined previous subtyping efforts and identified three robust RSS, RSS1/2/3 . These subtypes displayed promising results regarding their prognostic power in rectal cancer. We demonstrated differences in disease biology between RSS subtypes using an in-house cohort of rectal cancers analysed by a multiplex imaging platform. Our findings shed light on the molecular features of rectal cancers and suggest novel subtyping could benefit cancer prognosis.  \nMETHODS Samples  \nIn total, we","cbCaim8usDS4DTQQ","https://ap.wps.com/l/cbCaim8usDS4DTQQ","pdf",2392863,"English","# Background\n# Methods\n## Samples\n# Results\n# Conclusions","[{\"question\":\"Why are colon and rectal cancer subtyping methods not directly interchangeable?\",\"answer\":\"Existing colorectal subtyping methods were generated without strongly considering expression differences between colon and rectal tissues. The study also notes that neoadjuvant chemoradiotherapy can significantly impact rectal cancer gene expression.\"},{\"question\":\"What effect did neoadjuvant chemoradiotherapy have on CMS subtypes in rectal cancers?\",\"answer\":\"Neoadjuvant chemoradiotherapy exposure produced a strong shift in CMS subtypes in rectal cancers, indicating treatment can change the molecular subtype distribution.\"},{\"question\":\"How many rectal cancer-specific subtypes were identified, and what distinguishes them?\",\"answer\":\"Three robust RSS were identified. RSS1 has better disease-free survival with high MYC target gene expression and low angiogenesis activity; RSS2 has worse survival with low regulatory T cells, strong EMT/angiogenesis signaling, and high TGF-β, NF-κB, and TNF-α activation; RSS3 shows deactivation of EGFR, MAPK, and WNT pathways.\"}]","Identification of unique rectal cancer-specific subtypes | PDF",1789996785,25]