2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T7e7,Colorectal cancer (CRC) remains a leading cause of cancer mortality worldwide, with clinical progress limited by intratumoural cellular diversity and the absence of robust, informative markers. Leveraging the heterogeneity of cancer-associated fibroblasts (CAFs) within the tumour microenvironment, this study aims to identify and evaluate candidate biomarkers to support patient stratification and improve prediction of therapeutic responses. We applied a multiomic approach integrating single-cell RNA sequencing, computational cell deconvolution and protein-level assessment from patient tumours, complemented by in vitro and in vivo preclinical models, to characterise stromal populations linked to CRC progression and treatment resistance. Retrospective analysis of over 3000 patient samples across multiple cohorts identified a distinct subset of CAFs expressing collagen triple helix repeat containing 1 (CTHRC1). CTHRC1(+) CAFs were associated with increased transforming growth factor-beta (TGF-beta) signalling and poor clinical outcomes in early and advanced disease stages. CTHRC1(+) CAFs enabled stratification of both mismatch repair-deficient/microsatellite instability (dMMR/MSI) and mismatch repair-proficient/microsatellite stability (pMMR/MSS) tumours into immune-inflamed and poorly immunogenic subtypes. Retrospective analysis of several clinical trials revealed that CTHRC1(+) CAFs are linked to resistance to immune checkpoint inhibitors in MSI and MSS tumours, suggesting therapeutic potential for combining TGF-beta blockade with immunotherapy. CTHRC1-expressing CAFs represent clinically relevant biomarkers that link molecular profiling with diagnostic pathology. Our findings support the potential incorporation of CTHRC1(+) CAF assessment into routine histopathological workflows, pending prospective validation, and suggest a framework for stroma-informed CRC stratification, particularly in patients with stroma-rich, treatment-resistant tumours and pMMR/MSS with limited therapeutic options.31:Tac5, Background Colorectal cancer (CRC) remains a leading cause of cancer mortality worldwide, with clinical progress limited by intratumoural cellular diversity and the absence of robust, informative markers. Objective Leveraging the heterogeneity of cancer-associated fibroblasts (CAFs) within the tumour microenvironment, this study aims to identify and evaluate candidate biomarkers to support patient stratification and improve prediction of therapeutic responses. Design We applied a multiomic approach integrating single-cell RNA sequencing, computational cell deconvolution and protein-level assessment from patient tumours, complemented by in vitro and in vivo preclinical models, to characterise stromal populations linked to CRC progression and treatment resistance. Results Retrospective analysis of over 3000 patient samples across multiple cohorts identified a distinct subset of CAFs expressing collagen triple helix repeat containing 1 (CTHRC1). CTHRC1(+) CAFs were associated with increased transforming growth factor-beta (TGF-beta) signalling and poor clinical outcomes in early and advanced disease stages. CTHRC1(+) CAFs enabled stratification of both mismatch repair-deficient/microsatellite instability (dMMR/MSI) and mismatch repair-proficient/microsatellite stability (pMMR/MSS) tumours into immune-inflamed and poorly immunogenic subtypes. Retrospective analysis of several clinical trials revealed that CTHRC1(+) CAFs are linked to resistance to immune checkpoint inhibitors in MSI and MSS tumours, suggesting therapeutic potential for combining TGF-beta blockade with immunotherapy. Conclusion CTHRC1-expressing CAFs represent clinically relevant biomarkers that link molecular profiling with diagnostic pathology. Our findings support the potential incorporation of CTHRC1(+) CAF assessment into routine histopathological workflows, pending prospective validation, and suggest a framework for stroma-informed CRC stratification, particularly in patients with stroma-rich, treatment-resistant tumours and pMMR/MSS with limited therapeutic options. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Biomarker / Stromal Profiling: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Biomarker / Stromal Profiling (modality). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/modality/Biomarker%20%2F%20Stromal%20Profiling\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Modalities\",\"item\":\"https://www.reachrx.ai/hub/tag/modality\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Biomarker / Stromal Profiling\",\"item\":\"https://www.reachrx.ai/hub/tag/modality/Biomarker%20%2F%20Stromal%20Profiling\"}]}}"}}]],["$","$L2f",null,{"title":"Biomarker / Stromal Profiling: Research & Clinical Takeaways","description":"Review evidence by treatment modality: Biomarker / Stromal Profiling — concise summaries and practical next steps.","papers":[{"doi":"10.1136/gutjnl-2025-336804","pmid":"41980760","title":"Stromal biomarker-based framework for identifying pMMR/MSS and dMMR/MSI colorectal cancers with poor outcomes and limited benefit from immunotherapy","journal_title":"Gut","journal_issn":"0017-5749","published_at":"2026-04-15T00:00:00.000Z","url":"https://doi.org/10.1136/gutjnl-2025-336804","source_score":68,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-04-20","doi":"10.1136/gutjnl-2025-336804","days":"30","issn":"0017-5749","rank":"5","field":"Clinical Medicine","score":"68","category":"Gastroenterology & Hepatology","categories":["Gastroenterology & Hepatology"],"_categories":["Gastroenterology & Hepatology"]},"pubmed":{"doi":"10.1136/gutjnl-2025-336804","title":"Stromal biomarker-based framework for identifying pMMR/MSS and dMMR/MSI colorectal cancers with poor outcomes and limited benefit from immunotherapy.","journal":"Gut","methods":"","results":"Retrospective analysis of over 3000 patient samples across multiple cohorts identified a distinct subset of CAFs expressing collagen triple helix repeat containing 1 (CTHRC1). CTHRC1(+) CAFs were associated with increased transforming growth factor-beta (TGF-beta) signalling and poor clinical outcomes in early and advanced disease stages. CTHRC1(+) CAFs enabled stratification of both mismatch repair-deficient/microsatellite instability (dMMR/MSI) and mismatch repair-proficient/microsatellite stability (pMMR/MSS) tumours into immune-inflamed and poorly immunogenic subtypes. Retrospective analysis of several clinical trials revealed that CTHRC1(+) CAFs are linked to resistance to immune checkpoint inhibitors in MSI and MSS tumours, suggesting therapeutic potential for combining TGF-beta blockade with immunotherapy.","abstract":"$30","keywords":["BIOMARKERS","COLORECTAL CANCER","IMMUNOHISTOPATHOLOGY","MYOFIBROBLASTS"],"pubmed_id":"41980760","conclusions":"CTHRC1-expressing CAFs represent clinically relevant biomarkers that link molecular profiling with diagnostic pathology. Our findings support the potential incorporation of CTHRC1(+) CAF assessment into routine histopathological workflows, pending prospective validation, and suggest a framework for stroma-informed CRC stratification, particularly in patients with stroma-rich, treatment-resistant tumours and pMMR/MSS with limited therapeutic options.","publication_date":"2026-04-15T00:00:00"},"crossref":{"DOI":"10.1136/gutjnl-2025-336804","URL":"https://doi.org/10.1136/gutjnl-2025-336804","ISSN":["0017-5749","1468-3288"],"link":[{"URL":"https://syndication.highwire.org/content/doi/10.1136/gutjnl-2025-336804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"gutjnl-2025-336804","type":"journal-article","issue":null,"score":1,"title":["Stromal biomarker-based framework for identifying pMMR/MSS and dMMR/MSI colorectal cancers with poor outcomes and limited benefit from immunotherapy"],"author":[{"given":"Mar","family":"Iglesias Coma","sequence":"first","affiliation":[{"name":"Department of Pathology, Hospital del Mar, Barcelona, Spain"},{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"},{"name":"Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain"}]},{"given":"Jordi","family":"Badia-Ramentol","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"}]},{"given":"Carolina","family":"Martinez-Ciarpaglini","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Clínico Universitario, University of Valencia, Valencia, Spain"},{"name":"INCLIVA Biomedical Research Institute, Valencia, Spain"}]},{"given":"Jenniffer","family":"Linares","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"},{"name":"Department of Medical Oncology, Hospital del Mar, Barcelona, Spain"}]},{"given":"Noelia","family":"Tarazona","sequence":"additional","affiliation":[{"name":"Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"INCLIVA Biomedical Research Institute, Valencia, Spain"},{"name":"Department of Medical Oncology, Hospital Clinico Universitario, University of Valencia, Valencia, Spain"}]},{"given":"Nuria","family":"Mulet-Margalef","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Catalan Institute of Oncology (ICO) Badalona, Badalona, Spain"},{"name":"Germans Trias I Pujol Research Institute (IGTP), Badalona, Spain"}]},{"given":"Paula","family":"Tornero-Piñero","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital del Mar, Barcelona, Spain"}]},{"given":"Anna","family":"Sallent-Aragay","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"}]},{"given":"Alba","family":"Recort-Bascuas","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"}]},{"given":"Joan","family":"Gibert","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"}]},{"given":"Marta","family":"Sant-Albors","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"}]},{"given":"Daniele V F","family":"Tauriello","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain"},{"name":"Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands"}]},{"given":"Melba","family":"Cruz-Moral","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"}]},{"given":"Marina","family":"Carreras-Gallardo","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"}]},{"given":"Elena","family":"Sancho","sequence":"additional","affiliation":[{"name":"Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain"}]},{"given":"Clara","family":"Morral Martinez","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain"}]},{"given":"Marta","family":"Garrido","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"}]},{"given":"Jose Luis Manzano","family":"Mozo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Catalan Institute of Oncology (ICO) Badalona, Badalona, Spain"},{"name":"Germans Trias I Pujol Research Institute (IGTP), Badalona, Spain"}]},{"given":"Andrés","family":"Cervantes","sequence":"additional","affiliation":[{"name":"Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"INCLIVA Biomedical Research Institute, Valencia, Spain"},{"name":"Department of Medical Oncology, Hospital Clinico Universitario, University of Valencia, Valencia, Spain"}]},{"given":"Clara","family":"Montagut","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"},{"name":"Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Department of Medical Oncology, Hospital del Mar, Barcelona, Spain"},{"name":"Pompeu Fabra University, Barcelona, Spain"}]},{"given":"Eduard","family":"Batlle","sequence":"additional","affiliation":[{"name":"Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain"},{"name":"Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain"},{"name":"Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona, Spain"}]},{"given":"Alexandre","family":"Calon","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Hospital del Mar Research Institute (HMRIB), Barcelona, Spain"}]}],"funder":[{"id":[{"id":"10.13039/501100004587","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100004587","name":"Instituto de Salud Carlos III","award":["CPII21/00012"],"award-info":[{"award-number":["CPII21/00012"]}],"doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/501100004587","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100004587","name":"Instituto de Salud Carlos III","award":["PI20/00011"],"award-info":[{"award-number":["PI20/00011"]}],"doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/501100004587","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100004587","name":"Instituto de Salud Carlos III","award":["PI23/00599"],"award-info":[{"award-number":["PI23/00599"]}],"doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/501100004587","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100004587","name":"Instituto de Salud Carlos III","award":["PT20/00023"],"award-info":[{"award-number":["PT20/00023"]}],"doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/501100002704","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100002704","name":"Fundación Científica Asociación Española Contra el Cáncer","award":["LABAE235294CALO"],"award-info":[{"award-number":["LABAE235294CALO"]}],"doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/501100002704","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100002704","name":"Fundación Científica Asociación Española Contra el Cáncer","award":["PROYE18046BATL2"],"award-info":[{"award-number":["PROYE18046BATL2"]}],"doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/501100011033","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100011033","name":"Agencia Estatal de Investigación","award":["CNS2023-145267"],"award-info":[{"award-number":["CNS2023-145267"]}],"doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/501100003030","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100003030","name":"Agència de Gestió d’Ajuts Universitaris i de Recerca","award":["2021 SGR 001278"],"award-info":[{"award-number":["2021 SGR 001278"]}],"doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2026,4,14]]},"member":"239","prefix":"10.1136","source":"Crossref","volume":null,"created":{"date-time":"2026-04-14T11:20:11Z","timestamp":1776165611000,"date-parts":[[2026,4,14]]},"indexed":{"date-time":"2026-04-14T12:02:49Z","timestamp":1776168169178,"date-parts":[[2026,4,14]]},"license":[{"URL":"https://creativecommons.org/licenses/by-nc/4.0/","start":{"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000,"date-parts":[[2026,4,14]]},"delay-in-days":0,"content-version":"unspecified"}],"subject":[],"abstract":"$31","accepted":{"date-parts":[[2026,2,14]]},"language":"en","relation":{},"resource":{"primary":{"URL":"https://gut.bmj.com/lookup/doi/10.1136/gutjnl-2025-336804"}},"subtitle":[],"deposited":{"date-time":"2026-04-14T11:20:16Z","timestamp":1776165616000,"date-parts":[[2026,4,14]]},"issn-type":[{"type":"print","value":"0017-5749"},{"type":"electronic","value":"1468-3288"}],"published":{"date-parts":[[2026,4,14]]},"publisher":"BMJ","reference":[{"DOI":null,"key":"2026041404200581000_gutjnl-2025-336804v1.1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Amin M , Edge S , Greene F , et al . AJCC cancer staging manual. 8th edn. New York: Springer International Publishing, 2017.","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1038/s41575-020-0275-y","key":"2026041404200581000_gutjnl-2025-336804v1.2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.annonc.2020.06.022","key":"2026041404200581000_gutjnl-2025-336804v1.3","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s43018-025-00960-z","key":"2026041404200581000_gutjnl-2025-336804v1.4","year":"2025","issue":null,"author":"Martín-Arana","volume":"6","first-page":"1000","unstructured":null,"article-title":"Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer","journal-title":"Nat Cancer","doi-asserted-by":"crossref"},{"DOI":"10.1136/jclinpath-2014-202467","key":"2026041404200581000_gutjnl-2025-336804v1.5","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":null,"key":"2026041404200581000_gutjnl-2025-336804v1.6","year":"2015","issue":null,"author":"Al-Shamsi","volume":"6","first-page":"314","unstructured":null,"article-title":"Extended RAS testing in metastatic colorectal cancer-Refining the predictive molecular biomarkers","journal-title":"J Gastrointest Oncol","doi-asserted-by":null},{"DOI":null,"key":"2026041404200581000_gutjnl-2025-336804v1.7","year":"2019","issue":null,"author":"Taieb","volume":"79","first-page":"1375","unstructured":null,"article-title":"The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer","journal-title":"Drugs (Abingdon Engl)","doi-asserted-by":null},{"DOI":"10.1056/NEJMoa1500596","key":"2026041404200581000_gutjnl-2025-336804v1.8","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3390/cancers15041022","key":"2026041404200581000_gutjnl-2025-336804v1.9","year":"2023","issue":null,"author":"Mulet-Margalef","volume":"15","first-page":null,"unstructured":null,"article-title":"Challenges and Therapeutic Opportunities in the dMMR/MSI-H Colorectal Cancer Landscape","journal-title":"Cancers (Basel)","doi-asserted-by":"crossref"},{"DOI":"10.1053/j.gastro.2009.12.064","key":"2026041404200581000_gutjnl-2025-336804v1.10","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1002/cncr.29190","key":"2026041404200581000_gutjnl-2025-336804v1.11","year":"2015","issue":null,"author":"Moreira","volume":"121","first-page":"1395","unstructured":null,"article-title":"Prevalence of somatic mutl homolog 1 promoter hypermethylation in Lynch syndrome colorectal cancer","journal-title":"Cancer","doi-asserted-by":"crossref"},{"DOI":"10.1056/NEJMra0804588","key":"2026041404200581000_gutjnl-2025-336804v1.12","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41571-025-01015-z","key":"2026041404200581000_gutjnl-2025-336804v1.13","year":"2025","issue":null,"author":"Ambrosini","volume":"22","first-page":"385","unstructured":null,"article-title":"Epidemiology, pathogenesis, biology and evolving management of MSI-H/dMMR cancers","journal-title":"Nat Rev Clin Oncol","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41571-025-01054-6","key":"2026041404200581000_gutjnl-2025-336804v1.14","year":"2025","issue":null,"author":"Johannet","volume":"22","first-page":"734","unstructured":null,"article-title":"Therapeutic targeting of mismatch repair-deficient cancers","journal-title":"Nat Rev Clin Oncol","doi-asserted-by":"crossref"},{"DOI":"10.1200/JCO.19.02107","key":"2026041404200581000_gutjnl-2025-336804v1.15","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S1470-2045(17)30422-9","key":"2026041404200581000_gutjnl-2025-336804v1.16","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa2017699","key":"2026041404200581000_gutjnl-2025-336804v1.17","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41416-019-0599-y","key":"2026041404200581000_gutjnl-2025-336804v1.18","year":"2019","issue":null,"author":"Sahin","volume":"121","first-page":"809","unstructured":null,"article-title":"Immune checkpoint inhibitors for the treatment of MSI-H/MMR-D colorectal cancer and a perspective on resistance mechanisms","journal-title":"Br J Cancer","doi-asserted-by":"crossref"},{"DOI":"10.1038/nature11252","key":"2026041404200581000_gutjnl-2025-336804v1.19","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/nm.3174","key":"2026041404200581000_gutjnl-2025-336804v1.20","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1371/journal.pmed.1001453","key":"2026041404200581000_gutjnl-2025-336804v1.21","year":"2013","issue":null,"author":"Marisa","volume":"10","first-page":null,"unstructured":null,"article-title":"Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value","journal-title":"PLoS Med","doi-asserted-by":"crossref"},{"DOI":"10.1038/nm.3175","key":"2026041404200581000_gutjnl-2025-336804v1.22","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/nm.3967","key":"2026041404200581000_gutjnl-2025-336804v1.23","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/annonc/mdy410","key":"2026041404200581000_gutjnl-2025-336804v1.24","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/annonc/mdz052","key":"2026041404200581000_gutjnl-2025-336804v1.25","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1200/JCO.18.02258","key":"2026041404200581000_gutjnl-2025-336804v1.26","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/annonc/mdz387","key":"2026041404200581000_gutjnl-2025-336804v1.27","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/annonc/mdz412","key":"2026041404200581000_gutjnl-2025-336804v1.28","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/ng.3224","key":"2026041404200581000_gutjnl-2025-336804v1.29","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41467-023-36334-1","key":"2026041404200581000_gutjnl-2025-336804v1.30","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/ng.3225","key":"2026041404200581000_gutjnl-2025-336804v1.31","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/nature25492","key":"2026041404200581000_gutjnl-2025-336804v1.32","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1186/s12964-023-01125-0","key":"2026041404200581000_gutjnl-2025-336804v1.33","year":"2023","issue":null,"author":"Zhao","volume":"21","first-page":null,"unstructured":null,"article-title":"What is new in cancer-associated fibroblast biomarkers?","journal-title":"Cell Commun Signal","doi-asserted-by":"crossref"},{"DOI":"10.1038/s12276-023-01013-0","key":"2026041404200581000_gutjnl-2025-336804v1.34","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41422-020-0355-0","key":"2026041404200581000_gutjnl-2025-336804v1.35","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41587-020-0439-x","key":"2026041404200581000_gutjnl-2025-336804v1.36","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1214/ss/1038425655","key":"2026041404200581000_gutjnl-2025-336804v1.37","year":"1996","issue":null,"author":"Eilers","volume":"11","first-page":"89","unstructured":null,"article-title":"Flexible smoothing with B-splines and penalties","journal-title":"Statist Sci","doi-asserted-by":"crossref"},{"DOI":"10.1073/pnas.0506580102","key":"2026041404200581000_gutjnl-2025-336804v1.38","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1007/978-1-0716-0327-7_17","key":"2026041404200581000_gutjnl-2025-336804v1.39","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41374-018-0057-0","key":"2026041404200581000_gutjnl-2025-336804v1.40","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41598-019-43492-0","key":"2026041404200581000_gutjnl-2025-336804v1.41","year":"2019","issue":null,"author":"Ragulan","volume":"9","first-page":null,"unstructured":null,"article-title":"Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes","journal-title":"Sci Rep","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41588-025-02380-2","key":"2026041404200581000_gutjnl-2025-336804v1.42","year":"2025","issue":null,"author":"Henriques","volume":"57","first-page":"3050","unstructured":null,"article-title":"TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1+ macrophages","journal-title":"Nat Genet","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.immuni.2019.03.024","key":"2026041404200581000_gutjnl-2025-336804v1.43","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41467-022-32782-3","key":"2026041404200581000_gutjnl-2025-336804v1.44","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1126/science.1129139","key":"2026041404200581000_gutjnl-2025-336804v1.45","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3390/cancers13061281","key":"2026041404200581000_gutjnl-2025-336804v1.46","year":"2021","issue":null,"author":"El Sissy","volume":"13","first-page":"1","unstructured":null,"article-title":"Therapeutic Implications of the Immunoscore in Patients with Colorectal Cancer","journal-title":"Cancers (Basel)","doi-asserted-by":"crossref"},{"DOI":"10.23736/s1824-4785.20.03249-5","key":"2026041404200581000_gutjnl-2025-336804v1.47","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1001/jamaoncol.2021.0177","key":"2026041404200581000_gutjnl-2025-336804v1.48","year":"2021","issue":null,"author":"Sinicrope","volume":"7","first-page":"969","unstructured":null,"article-title":"Tumor-Infiltrating Lymphocytes for Prognostic Stratification in Nonmetastatic Colon Cancer-Are We There Yet?","journal-title":"JAMA Oncol","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41416-020-01048-4","key":"2026041404200581000_gutjnl-2025-336804v1.49","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1158/2159-8290.CD-14-0863","key":"2026041404200581000_gutjnl-2025-336804v1.50","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41573-018-0007-y","key":"2026041404200581000_gutjnl-2025-336804v1.51","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1158/1078-0432.CCR-15-2879","key":"2026041404200581000_gutjnl-2025-336804v1.52","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1158/1078-0432.CCR-22-3964","key":"2026041404200581000_gutjnl-2025-336804v1.53","year":"2023","issue":null,"author":"Gallois","volume":"29","first-page":"3771","unstructured":null,"article-title":"Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors","journal-title":"Clin Cancer Res","doi-asserted-by":"crossref"},{"DOI":"10.1053/j.gastro.2021.06.064","key":"2026041404200581000_gutjnl-2025-336804v1.54","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.annonc.2023.05.010","key":"2026041404200581000_gutjnl-2025-336804v1.55","year":"2023","issue":null,"author":"Ratovomanana","volume":"34","first-page":"703","unstructured":null,"article-title":"Prediction of response to immune checkpoint blockade in patients with metastatic colorectal cancer with microsatellite instability","journal-title":"Ann Oncol","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.annonc.2022.04.450","key":"2026041404200581000_gutjnl-2025-336804v1.56","year":"2022","issue":null,"author":"Luo","volume":"33","first-page":"824","unstructured":null,"article-title":"Deciphering radiological stable disease to immune checkpoint inhibitors","journal-title":"Ann Oncol","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41591-020-0805-8","key":"2026041404200581000_gutjnl-2025-336804v1.57","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/nature25501","key":"2026041404200581000_gutjnl-2025-336804v1.58","year":"2018","issue":null,"author":"Mariathasan","volume":"554","first-page":"544","unstructured":null,"article-title":"TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells","journal-title":"Nature New Biol","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41588-023-01355-5","key":"2026041404200581000_gutjnl-2025-336804v1.59","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.ccell.2021.05.009","key":"2026041404200581000_gutjnl-2025-336804v1.60","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41598-022-23319-1","key":"2026041404200581000_gutjnl-2025-336804v1.61","year":"2022","issue":null,"author":"Kang","volume":"12","first-page":null,"unstructured":null,"article-title":"A scoping review and meta-analysis on the prevalence of pan-tumour biomarkers (dMMR, MSI, high TMB) in different solid tumours","journal-title":"Sci Rep","doi-asserted-by":"crossref"},{"DOI":"10.3389/fcell.2020.621070","key":"2026041404200581000_gutjnl-2025-336804v1.62","year":"2021","issue":null,"author":"Linares","volume":"8","first-page":"621070","unstructured":null,"article-title":"Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy","journal-title":"Front Cell Dev Biol","doi-asserted-by":"crossref"},{"DOI":"10.1038/s41568-021-00413-6","key":"2026041404200581000_gutjnl-2025-336804v1.63","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.ccr.2012.08.013","key":"2026041404200581000_gutjnl-2025-336804v1.64","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.semcancer.2013.12.008","key":"2026041404200581000_gutjnl-2025-336804v1.65","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1136/jitc-2023-008409","key":"2026041404200581000_gutjnl-2025-336804v1.66","year":"2024","issue":null,"author":"Lenz","volume":"12","first-page":null,"unstructured":null,"article-title":"Modified FOLFOX6 plus bevacizumab with and without nivolumab for first-line treatment of metastatic colorectal cancer: phase 2 results from the CheckMate 9X8 randomized clinical trial","journal-title":"J Immunother Cancer","doi-asserted-by":"crossref"},{"DOI":"10.1016/S1470-2045(22)00274-1","key":"2026041404200581000_gutjnl-2025-336804v1.67","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.dld.2021.06.009","key":"2026041404200581000_gutjnl-2025-336804v1.68","year":"2021","issue":null,"author":"Gallois","volume":"53","first-page":"1254","unstructured":null,"article-title":"Pembrolizumab with Capox Bevacizumab in patients with microsatellite stable metastatic colorectal cancer and a high immune infiltrate: The FFCD 1703-POCHI trial","journal-title":"Dig Liver Dis","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.annonc.2024.06.005","key":"2026041404200581000_gutjnl-2025-336804v1.69","year":"2024","issue":null,"author":"Tougeron","volume":"35","first-page":null,"unstructured":null,"article-title":"LBA1 Pembrolizumab in combination with xelox and bevacizumab in patients with microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC) and a high immune infiltrate: A proof of concept study - Preliminary results of FFCD 1703 POCHI trial","journal-title":"Ann Oncol","doi-asserted-by":"crossref"},{"DOI":"10.1016/j.annonc.2020.07.009","key":"2026041404200581000_gutjnl-2025-336804v1.70","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"}],"short-title":[],"update-policy":"https://doi.org/10.1136/crossmarkpolicy","alternative-id":["10.1136/gutjnl-2025-336804"],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Gut"],"reference-count":70,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,4,14]]},"references-count":70,"clinical-trial-number":[{"registry":"10.18810/clinical-trials-gov","clinical-trial-number":"nct02423343"},{"registry":"10.18810/clinical-trials-gov","clinical-trial-number":"nct04501094"},{"registry":"10.18810/clinical-trials-gov","clinical-trial-number":"nct03436563"},{"registry":"10.18810/clinical-trials-gov","clinical-trial-number":"nct03620201"}],"short-container-title":["Gut"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1136/gutjnl-2025-336804","is_oa":true,"title":"Stromal biomarker-based framework for identifying pMMR/MSS and dMMR/MSI colorectal cancers with poor outcomes and limited benefit from immunotherapy","updated":"2026-04-15T08:25:23+00:00","published_date":"2026-04-14","best_oa_location":{"url":"https://doi.org/10.1136/gutjnl-2025-336804","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.1136/gutjnl-2025-336804"}}},"created_at":"2026-05-07T22:51:01.190Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"condition","value":"Colorectal Cancer","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"modality","value":"Biomarker / Stromal Profiling","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"modality","value":"TGF-β Inhibitor","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"sample_size","value":"n=3000+","value_numeric":3000},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"study_design","value":"Retrospective Cohort Study with Translational Multiomic Analysis","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"warning","value":"Impact flag 'practice_changing' applied cautiously — the authors themselves note prospective validation is still required before clinical implementation.","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"warning","value":"Publication date listed as 2026-04-14, which is in the future relative to standard indexing timelines; verified as provided in the source metadata.","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"warning","value":"Sample size of >3,000 is stated but exact N per cohort or trial is not broken out in the abstract — the integer 3,000 used as a floor estimate.","value_numeric":null},{"paper_doi":"10.1136/gutjnl-2025-336804","tag_type":"warning","value":"Study design label 'Retrospective Cohort Study with Translational Multiomic Analysis' is a composite; the paper combines retrospective clinical data with preclinical experiments, which does not map cleanly to a single canonical design.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated CTHRC1-expressing cancer-associated fibroblasts (CAFs) as stromal biomarkers in colorectal cancer (CRC), using a multiomic approach (single-cell RNA sequencing, computational deconvolution, protein-level assessment) across >3,000 patient samples from multiple cohorts, plus in vitro/in vivo models, to stratify both pMMR/MSS and dMMR/MSI tumours and predict immunotherapy response.","key_result":"CTHRC1(+) CAFs were associated with elevated TGF-β signalling, poor clinical outcomes across early and advanced disease stages, and resistance to immune checkpoint inhibitors in both MSI and MSS tumours; they enabled stratification of both MMR subtypes into immune-inflamed vs. poorly immunogenic groups.","limitations":"All clinical analyses were retrospective, including the clinical trial data; prospective validation is explicitly absent. The study does not report standardised cut-offs or assay protocols ready for immediate clinical adoption.","practice_takeaway":"Consider CTHRC1(+) CAF status as a potential stratification tool in CRC, especially for pMMR/MSS patients where immunotherapy options are limited — high CTHRC1(+) CAF burden may signal poor ICI benefit and flag candidates for TGF-β blockade combination strategies. Await prospective validation before routine use."}}],"initialOffset":1,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Biomarker / Stromal Profiling"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Biomarker / Stromal Profiling"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Biomarker / Stromal Profiling"}}}]]

Papers