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Nat Genet. 2015 Apr;47(4):312-9. doi: 10.1038/ng.3224. Epub 2015 Feb 23.

Stromal contribution to the colorectal cancer transcriptome.

Author information

1
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.
2
Department of Oncology, University of Torino, Candiolo, Italy.
3
Candiolo Cancer Institute, Fondazione Piemontese per l'Oncologia'Istituto di Ricovero e Cura a Carattere Scientifico (FRO-IRCCS), Candiolo, Italy.
4
Department of Medical Science, University of Torino, Torino, Italy.
5
Department of Oncology, University of Torino, Orbassano, Italy.
6
Department of Molecular Biotechnology and Health Science, Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy.
7
Institute of Oncology Prof. Dr. Ion Chiricuta, Cluj, Romania.
8
Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.

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.

PMID:
25706627
DOI:
10.1038/ng.3224
[Indexed for MEDLINE]
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