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

Claudio Isella, Francesco Brundu, Sara E. Bellomo, Francesco Galimi, Eugenia Zanella, Roberta Porporato, Consalvo Petti, Alessandro Fiori, Francesca Orzan, Rebecca Senetta, Carla Boccaccio, Elisa Ficarra, Luigi Marchionni, Livio Trusolino (), Enzo Medico () and Andrea Bertotti ()
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Claudio Isella: University of Torino School of Medicine
Francesco Brundu: Torino School of Engineering
Sara E. Bellomo: University of Torino School of Medicine
Francesco Galimi: University of Torino School of Medicine
Eugenia Zanella: Candiolo Cancer Institute—FPO IRCCS
Roberta Porporato: Candiolo Cancer Institute—FPO IRCCS
Consalvo Petti: University of Torino School of Medicine
Alessandro Fiori: Candiolo Cancer Institute—FPO IRCCS
Francesca Orzan: University of Torino School of Medicine
Rebecca Senetta: Candiolo Cancer Institute—FPO IRCCS
Carla Boccaccio: University of Torino School of Medicine
Elisa Ficarra: Torino School of Engineering
Luigi Marchionni: Johns Hopkins University
Livio Trusolino: University of Torino School of Medicine
Enzo Medico: University of Torino School of Medicine
Andrea Bertotti: University of Torino School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: 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-β 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.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15107

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DOI: 10.1038/ncomms15107

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