{"entity":{"id":"paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015","kind":"paper","name":"Stromal gene expression defines poor-prognosis subtypes in colorectal cancer","aka":[],"tldr":"Published beside the paper above and reaching the same conclusion from the other direction: the prognostic power of every published bowel cancer classification comes from the scar-forming cells, and TGF-beta is what makes them dangerous.","summary":"On evaluating recent molecular classifications of colorectal cancer, the authors found that their predictive power arises from genes expressed by stromal cells rather than epithelial tumour cells. Bioinformatic and immunohistochemical analyses identified stromal markers that associate robustly with disease relapse across the various classifications. Functional studies showed that cancer-associated fibroblasts increase the frequency of tumour-initiating cells, an effect dramatically enhanced by TGF-beta signalling, and that all poor-prognosis subtypes share a gene programme induced by TGF-beta in tumour stromal cells. In patient-derived tumour organoids and xenografts, TGF-beta signalling inhibitors blocking the cross-talk between cancer cells and the microenvironment halted disease progression.","asOf":"2026-09-24","links":[{"label":"Calon et al., Nat Genet 2015: stromal gene expression defines the poor-prognosis subtypes of colorectal cancer","url":"https://doi.org/10.1038/ng.3225"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25706628/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["organoids","rna-seq"],"targets":["tgfb1","tgfbr2"],"drugs":[],"companies":[],"institutions":[],"pathways":["tgf-beta","caf-activation-desmoplasia","cancer-stem-cells-plasticity"],"terms":["cms-subtypes","desmoplasia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2015,"doi":"10.1038/ng.3225","pmid":"25706628","authors":"Calon A, Lonardo E, Berenguer-Llergo A, et al.","paperType":"translational","findings":["Predictive power of published classifications arises from stromal, not epithelial, genes.","Fibroblasts increase tumour-initiating cell frequency, dramatically enhanced by TGF-beta.","TGF-beta inhibition halted progression in organoids and xenografts."],"whatItMeans":"It made TGF-beta the central target of the microsatellite-stable half of the disease, which is the line that leads to Tauriello's immune-evasion work and to the TGF-beta plus checkpoint combinations in trials.","caveats":["Model systems; no TGF-beta inhibitor has an approval in colorectal cancer.","Stromal signatures are sensitive to sampling and to how much tumour was in the section."],"changedPractice":false},"route":"/key-papers/paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"organoids","kind":"technology","name":"Patient-derived organoids","route":"/technologies/organoids/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"target":[{"id":"tgfb1","kind":"target","name":"TGFB1","route":"/targets/tgfb1/"},{"id":"tgfbr2","kind":"target","name":"TGFBR2","route":"/targets/tgfbr2/"}],"pathway":[{"id":"cancer-stem-cells-plasticity","kind":"pathway","name":"Cancer stem cells & phenotypic plasticity","route":"/pathways/cancer-stem-cells-plasticity/"},{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"}],"term":[{"id":"cms-subtypes","kind":"term","name":"Consensus molecular subtypes (CMS1-4)","route":"/terms/cms-subtypes/"},{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"},{"id":"mss-pmmr","kind":"term","name":"Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR)","route":"/terms/mss-pmmr/"}],"journal":[{"id":"nature-genetics","kind":"journal","name":"Nature Genetics","route":"/journals/nature-genetics/"}]}}