期刊
CLINICAL CANCER RESEARCH
卷 21, 期 7, 页码 1688-1698出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-14-0432
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资金
- MD Anderson Cancer Center Support Grant [1CA16672]
- Dan L. Duncan Cancer Center Support Grant
- Baylor College of Medicine
- Susan G. Komen Promise Grant [KG081694]
Purpose: Genomic profiling studies suggest triple-negative breast cancer (TNBC) is a heterogeneous disease. In this study we sought to define TNBC subtypes and identify subtype-specific markers and targets. Experimental Design: RNA and DNA profiling analyses were conducted on 198 TNBC tumors (ER-negativity defined as Allred Scale value <= 2) with >50% cellularity (discovery set: n=84; validation set: n=114) collected at Baylor College of Medicine. An external data set of 7 publically-accessible TNBC studies was used to confirm results. DNA copy number, disease-free survival (DFS) and disease-specific survival (DSS) were analyzed independently using these datasets. Results: We identified and confirmed four distinct TNBC subtypes: (1) Luminal-AR (LAR); 2) Mesenchymal (MES); 3) Basal-Like Immune-Suppressed (BLIS), and 4) Basal-Like Immune-Activated (BLIA). Of these, prognosis is worst for BLIS tumors and best for BLIA tumors for both DFS (logrank test p=0.042 and 0.041, respectively) and DSS (logrank test p=0.039 and 0.029, respectively). DNA copy number analysis produced two major groups (LAR and MES/BLIS/BLIA), and suggested gene amplification drives gene expression in some cases (FGFR2 (BLIS)). Putative subtype-specific targets were identified: 1) LAR: androgen receptor and the cell surface mucin MUC1; 2) MES: growth factor receptors (PDGF receptor A; c-Kit); 3) BLIS: an immune suppressing molecule (VTCN1); and 4) BLIA: Stat signal transduction molecules and cytokines. Conclusions: There are four stable TNBC subtypes characterized by the expression of distinct molecular profiles that have distinct prognoses. These studies identify novel subtype-specific targets that can be targeted in the future for effective treatment of TNBCs. (C)2014 AACR.
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