Stromal contribution to the colorectal cancer transcriptome.
Claudio IsellaAndrea TerrasiSara Erika BellomoConsalvo PettiGiovanni GalatolaAndrea MuratoreAlfredo MellanoRebecca SenettaAdele CassentiCristina SonettoGiorgio InghiramiLivio TrusolinoZsolt FeketeMark De RidderPaola CassoniGuy StormeAndrea BertottiEnzo MedicoPublished in: Nature genetics (2015)
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.
Keyphrases
- poor prognosis
- long non coding rna
- endothelial cells
- bone marrow
- genome wide
- gene expression
- rectal cancer
- transcription factor
- early stage
- electronic health record
- binding protein
- squamous cell carcinoma
- dna methylation
- locally advanced
- heat shock
- big data
- vascular endothelial growth factor
- peripheral blood
- radiation induced
- rna seq
- induced pluripotent stem cells
- high glucose
- extracellular matrix
- single cell
- genome wide identification