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-beta pathway activity, epithelial-mesenchymal transition, poor prognosis; (iii) CRIS-C: elevated EGFR signalling, sensitivity to EGFR inhibitors; (iv) CRIS-D: WNTactivation, 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.

Selective analysis of cancer-cell intrinsic transcriptional traits defines novel clinically relevant subtypes of colorectal cancer

ISELLA, CLAUDIO;BELLOMO, SARA ERIKA;GALIMI, Francesco;ZANELLA, Eugenia Rosalinda;PETTI, CONSALVO;ORZAN, FRANCESCA NOEMI;SENETTA, REBECCA;BOCCACCIO, Carla;TRUSOLINO, Livio
;
MEDICO, Enzo
Co-last
;
BERTOTTI, Andrea
Co-last
2017

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-beta pathway activity, epithelial-mesenchymal transition, poor prognosis; (iii) CRIS-C: elevated EGFR signalling, sensitivity to EGFR inhibitors; (iv) CRIS-D: WNTactivation, 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.
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http://www.nature.com/ncomms/index.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499209/
Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all)
Isella, Claudio; Brundu, Francesco; Bellomo, Sara E.; Galimi, Francesco; Zanella, Eugenia; Porporato, Roberta; Petti, Consalvo; Fiori, Alessandro; Orzan, Francesca; Senetta, Rebecca; Boccaccio, Carla; Ficarra, Elisa; Marchionni, Luigi; Trusolino, Livio; Medico, Enzo; Bertotti, Andrea
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1642129
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