Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome

被引:292
作者
Bergamaschi, A. [1 ]
Tagliabue, E. [2 ]
Sorlie, T. [1 ,3 ]
Naurne, B. [4 ]
Triulzi, T. [2 ]
Orlandi, R. [2 ]
Russnes, H. G. [5 ]
Nesland, J. M. [5 ,6 ]
Tammi, R. [7 ]
Auvinen, P. [8 ]
Kosma, V-M [9 ]
Menard, S. [2 ]
Borresen-Dale, A-L [1 ,6 ]
机构
[1] Natl Hosp Norway, Radiumhosp, Canc Res Inst, Med Ctr,Dept Genet, N-0310 Oslo, Norway
[2] Natl Canc Inst, Dept Expt Oncol, Milan, Italy
[3] Univ Oslo, Inst Informat, Fac Math & Nat Sci, N-0316 Oslo, Norway
[4] Natl Hosp Norway, Radiumhosp, Med Ctr, Canc Clin,Dept Oncol, Oslo, Norway
[5] Natl Hosp Norway, Radiumhosp, Med Ctr, Canc Clin,Dept Pathol, Oslo, Norway
[6] Univ Oslo, Fac Med, N-0316 Oslo, Norway
[7] Univ Kuopio, Dept Biomed Anat, Kuopio, Finland
[8] Kuopio Univ Hosp, Dept Oncol, Kuopio, Finland
[9] Univ Kuopio, Kuopio Univ Hosp, Inst Clin Med Pathol & Forens Med, Kuopio, Finland
关键词
breast cancer; gene expression profile; extracellular matrix; HIC;
D O I
10.1002/path.2278
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Prediction of the clinical outcome of breast cancer is multi-faceted and challenging. There is growing evidence that the complexity of the tumour micro-environment, consisting of several cell types and a complex mixture of proteins, plays an important role in development, progression, and response to therapy. In the current study, we investigated whether invasive breast tumours can be classified on the basis of the expression of extracellular matrix (ECM) components and whether such classification is representative of different clinical outcomes. We first examined the matrix composition of 28 primary breast carcinomas by morphology and gene expression profiling using 22K oligonucleotide Agilent microarrays. Hierarchical clustering of the gene expression profile of 278 ECM-related genes derived from the literature divided the tumours into four main groups (ECM1-4). A set of selected differentially expressed genes was validated by immunohistochemistry. The robustness of the ECM classification was confirmed by studying the four ECM groups in a previously published gene expression data set of 114 early-stage primary breast carcinomas profiled using cDNA arrays. Univariate survival analysis showed significant differences in clinical outcome among the various ECM subclasses. One set of tumours, designated ECM4, had a favourable outcome and was defined by the overexpression of a set of protease inhibitors belonging to the serpin family, while tumours with an ECM1 signature had a poorer prognosis and showed high expression of integrins and metallopeptidases, and low expression of several laminin chains. Furthermore, we identified three surrogate markers of ECM1 tumours: MARCO, PUNC, and SPARC, whose expression levels were associated with breast cancer survival and risk of recurrence. Our findings suggest that primary breast tumours can be classified based upon ECM composition and that this classification provides relevant information on the biology of breast carcinomas, further supporting the hypothesis that clinical outcome is strongly related to stromal characteristics. Copyright (C) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
引用
收藏
页码:357 / 367
页数:11
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