title: Stromal contribution to the colorectal cancer transcriptome.
abstract: Recent studies identified a poor-prognosis stem/serrated/mesenchymal (SSM) transcriptional subtype of colorectal cancer (CRC). We noted that genes upregulated in this subtype are also prominently expressed by stromal cells, suggesting that SSM transcripts could derive from stromal rather than epithelial cancer cells. To test this hypothesis, we analyzed CRC expression data from patient-derived xenografts, where mouse stroma supports human cancer cells. Species-specific expression analysis showed that the mRNA levels of SSM genes were mostly due to stromal expression. Transcriptional signatures built to specifically report the abundance of cancer-associated fibroblasts (CAFs), leukocytes or endothelial cells all had significantly higher expression in human CRC samples of the SSM subtype. High expression of the CAF signature was associated with poor prognosis in untreated CRC, and joint high expression of the stromal signatures predicted resistance to radiotherapy in rectal cancer. These data show that the distinctive transcriptional and clinical features of the SSM subtype can be ascribed to its particularly abundant stromal component.
authors.affiliation: 1] Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy. [2] Department of Oncology, University of Torino, Candiolo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Isella
authors.affiliation: Department of Oncology, University of Torino, Candiolo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Terrasi
authors.affiliation: 1] Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy. [2] Department of Oncology, University of Torino, Candiolo, Italy.
authors.forename: Sara Erika
authors.initials: SE
authors.lastname: Bellomo
authors.affiliation: Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy.
authors.forename: Consalvo
authors.initials: C
authors.lastname: Petti
authors.affiliation: Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Galatola
authors.affiliation: Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Muratore
authors.affiliation: Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mellano
authors.affiliation: Department of Medical Science, University of Torino, Torino, Italy.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Senetta
authors.affiliation: Department of Medical Science, University of Torino, Torino, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Cassenti
authors.affiliation: Department of Oncology, University of Torino, Orbassano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sonetto
authors.affiliation: Department of Molecular Biotechnology and Health Science, Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.affiliation: 1] Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy. [2] Department of Oncology, University of Torino, Candiolo, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Trusolino
authors.affiliation: Institute of Oncology Prof. Dr. Ion Chiricuta, Cluj, Romania.
authors.forename: Zsolt
authors.identifier: 0000000333868263
authors.initials: Z
authors.lastname: Fekete
authors.affiliation: Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Mark
authors.initials: M
authors.lastname: De Ridder
authors.affiliation: Department of Medical Science, University of Torino, Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
authors.affiliation: Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Storme
authors.affiliation: 1] Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy. [2] Department of Oncology, University of Torino, Candiolo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bertotti
authors.affiliation: 1] Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy. [2] Department of Oncology, University of Torino, Candiolo, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Medico
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D051379:Mice; D046228:Microarray Analysis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor