Stromal contribution to the colorectal cancer transcriptome

被引：372

作者：

Isella, Claudio ^{[1
,2
]}

Terrasi, Andrea ^{[2
]}

Bellomo, Sara Erika ^{[1
,2
]}

Petti, Consalvo ^{[1
]}

Galatola, Giovanni ^{[1
]}

Muratore, Andrea ^{[1
]}

Mellano, Alfredo ^{[1
]}

Senetta, Rebecca ^{[3
]}

Cassenti, Adele ^{[3
]}

Sonetto, Cristina ^{[4
]}

Inghirami, Giorgio ^{[5
]}

Trusolino, Livio ^{[1
,2
]}

Fekete, Zsolt ^{[6
]}

De Ridder, Mark ^{[7
]}

Cassoni, Paola

Storme, Guy ^{[7
]}

Bertotti, Andrea ^{[1
,2
]}

Medico, Enzo ^{[1
,2
]}

机构：

[1] Fdn Piemontese Oncol, Ist Ricovero & Cura Carattere Sci FRO IRCCS, Candiolo Canc Inst, Candiolo, Italy

[2] Univ Turin, Dept Oncol, Candiolo, Italy

[3] Univ Turin, Dept Med Sci, Turin, Italy

[4] Univ Turin, Dept Oncol, Orbassano, Italy

[5] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Ctr Expt Res & Med Studies, Turin, Italy

[6] Inst Oncol Prof Dr Ion Chiricuta, Cluj Napoca, Romania

[7] Vrije Univ Brussel, Univ Ziekenhuis Brussel, Dept Radiotherapy, Brussels, Belgium

来源：

NATURE GENETICS | 2015年 / 47卷 / 04期

关键词：

FIBROBLAST ACTIVATION PROTEIN; GENE-EXPRESSION; TUMOR XENOGRAFTS; POOR-PROGNOSIS; RECTAL-CANCER; HUMAN COLON; STEM-CELLS; RESISTANCE; HETEROGENEITY; RECURRENCE;

D O I：

10.1038/ng.3224

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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.

引用

页码：312 / U49

页数：11

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