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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.
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.
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.
Shares Consensus molecular subtypes (CMS1-4), Nature Genetics, Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness.
Shares TGFB1, Consensus molecular subtypes (CMS1-4), TGF-β signalling, Fibroblast activation, desmoplasia & matrix stiffness.
Shares TGFB1, Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR), TGF-β signalling, Colorectal cancer.
Shares Consensus molecular subtypes (CMS1-4), Desmoplasia (tumour stroma), RNA sequencing & expression profiling, Colorectal cancer.
Shares Nature Genetics, Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, RNA sequencing & expression profiling.
Shares TGFBR2, TGF-β signalling, Colorectal cancer.
Shares TGFB1, TGF-β signalling.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Patient-derived organoids.