Stromal gene expression defines poor-prognosis subtypes in colorectal cancer

被引：831

作者：

Calon, Alexandre ^{[1
]}

Lonardo, Enza ^{[1
]}

Berenguer-Llergo, Antonio ^{[1
]}

Espinet, Elisa ^{[1
]}

Hernando-Momblona, Xavier ^{[1
]}

Iglesias, Mar ^{[2
,3
,4
]}

Sevillano, Marta ^{[1
]}

Palomo-Ponce, Sergio ^{[1
]}

Tauriello, Daniele V. F. ^{[1
]}

Byrom, Daniel ^{[1
]}

Cortina, Carme ^{[1
]}

Morral, Clara ^{[1
]}

Barcelo, Carles ^{[1
]}

Tosi, Sebastien ^{[1
]}

Riera, Antoni ^{[1
]}

Attolini, Camille Stephan-Otto ^{[1
]}

Rossell, David ^{[1
]}

Sancho, Elena ^{[1
]}

Batlle, Eduard ^{[1
,5
]}

机构：

[1] Inst Res Biomed IRB Barcelona, Barcelona, Spain

[2] Hosp del Mar, Dept Pathol, Barcelona, Spain

[3] Hosp del Mar, Res Inst IMIM, Canc Res Program, Barcelona, Spain

[4] Univ Autonoma Barcelona, E-08193 Barcelona, Spain

[5] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain

来源：

NATURE GENETICS | 2015年 / 47卷 / 04期

关键词：

GROWTH-FACTOR-BETA; HUMAN-COLON; TGF-BETA; STEM-CELL; MOLECULAR SUBTYPES; TUMOR-GROWTH; GENOME; RECEPTOR; TUMORIGENESIS; METASTASIS;

D O I：

10.1038/ng.3225

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Recent molecular classifications of colorectal cancer (CRC) based on global gene expression profiles have defined subtypes displaying resistance to therapy and poor prognosis. Upon evaluation of these classification systems, we discovered that their predictive power arises from genes expressed by stromal cells rather than epithelial tumor cells. Bioinformatic and immunohistochemical analyses identify stromal markers that associate robustly with disease relapse across the various classifications. Functional studies indicate that cancer-associated fibroblasts (CAFs) increase the frequency of tumor-initiating cells, an effect that is dramatically enhanced by transforming growth factor (TGF)-beta signaling. Likewise, we find that all poor-prognosis CRC subtypes share a gene program induced by TGF-beta in tumor stromal cells. Using patient-derived tumor organoids and xenografts, we show that the use of TGF-beta signaling inhibitors to block the cross-talk between cancer cells and the microenvironment halts disease progression.

引用

页码：320 / U62

页数：13

共 54 条

[1]

[Anonymous], 1999, P ICONIP ANZIIS ANNE

[2] Gene expression omnibus: Microarray data storage, submission, retrieval, and analysis [J].