Selective analysis of cancer-cell intrinsic transcriptional traits defines novel clinically relevant subtypes of colorectal cancer
Abstract: Stromal content heavily impacts the transcriptional classification of colorectal cancer (CRC), with clinical and biological implications. Lineage-dependent stromal transcriptional components could therefore dominate over more subtle expression traits inherent to cancer cells. Since in patient-derived xenografts (PDXs) stromal cells of the human tumour are substituted by murine counterparts, here we deploy human-specific expression profiling of CRC PDXs to assess cancer-cell intrinsic transcriptional features. Through this approach, we identify five CRC intrinsic subtypes (CRIS) endowed with distinctive molecular, functional and phenotypic peculiarities: (i) CRIS-A: mucinous, glycolytic, enriched for microsatellite instability or KRAS mutations; (ii) CRIS-B: TGF-? pathway activity, epithelial–mesenchymal transition, poor prognosis; (iii) CRIS-C: elevated EGFR signalling, sensitivity to EGFR inhibitors; (iv) CRIS-D: WNT activation, IGF2 gene overexpression and amplification; and (v) CRIS-E: Paneth cell-like phenotype, TP53 mutations. CRIS subtypes successfully categorize independent sets of primary and metastatic CRCs, with limited overlap on existing transcriptional classes and unprecedented predictive and prognostic performances.
Citation:
Isella, Claudio; Brundu, FRANCESCO GAVINO; Bellomo, Sara E.; Galimi, Francesco; Zanella, Eugenia; Consalvo Petti, Roberta; Fiori, Alessandro; Orzan, Francesca; Senetta, Rebecca; Boccaccio, Carla; Ficarra, Elisa; Marchionni, Luigi; Trusolino, Livio; Medico, Enzo; Bertotti, Andrea "Selective analysis of cancer-cell intrinsic transcriptional traits defines novel clinically relevant subtypes of colorectal cancer" NATURE COMMUNICATIONS, vol. 8, pp. 1 -16 , 2017 DOI: 10.1038/ncomms15107
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- DOI: 10.1038/ncomms15107