Stromal contribution to the colorectal cancer transcriptome

Claudio Isella, Andrea Terrasi, Sara Erika Bellomo, Consalvo Petti, Giovanni Galatola, Andrea Muratore, Alfredo Mellano, Rebecca Senetta, Adele Cassenti, Cristina Sonetto, Giorgio Inghirami, Livio Trusolino, Zsolt Fekete, Mark De Ridder, Paola Cassoni, Guy Storme, Andrea Bertotti, Enzo Medico

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)312-319
Number of pages8
JournalNature Genetics
Volume47
Issue number4
DOIs
Publication statusPublished - Apr 28 2015

ASJC Scopus subject areas

  • Genetics
  • Medicine(all)

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    Isella, C., Terrasi, A., Bellomo, S. E., Petti, C., Galatola, G., Muratore, A., Mellano, A., Senetta, R., Cassenti, A., Sonetto, C., Inghirami, G., Trusolino, L., Fekete, Z., De Ridder, M., Cassoni, P., Storme, G., Bertotti, A., & Medico, E. (2015). Stromal contribution to the colorectal cancer transcriptome. Nature Genetics, 47(4), 312-319. https://doi.org/10.1038/ng.3224