Novel Degradome Markers in Breast Cancer
Microarray studies have identified several gene signatures that are associated with tumour metastasis or adverse outcome in several cancer types. Among these are the 17-gene solid tumour metastasis signature of Ramaswamy et al. (2003), the 70-gene good versus poor outcome predictor of van’t Veer et al. (2002), a wound response signature of Chang et al. (2004), and a 21-gene recurrence-score indicator in tamoxifen-treated node-negative breast cancer. These signatures show only moderate concordance, reflecting the complexity of the genetic pathways that contribute to malignancy. Unsurprisingly, degradome genes are represented in most of these predictors, and the utility of several more protease and related genes as biomarkers has been established by other profiling studies and functional analysis in model systems over the past few years. This chapter draws together information on key metalloproteinases and inhibitors that has emerged from array and quantitative real time polymerase chain reaction (qRT-PCR) analyses in the past few years, thereby highlighting candidates for further investigation. In particular, MMP1, MMP7, MMP9, MMP11, MMP23 and PLAUR (uPAR) have all featured in poor prognosis expression signatures, and MMP1 and MMP2 are included in a 4-gene determinant of breast metastasis to the lungs. Moreover, from qRT-PCR studies, MMP8 and ADAMTS15 are shown to be novel markers of good prognosis in breast cancer, whereas MMP11, ADAMTS8, ADAM 12 and ADAM28 are associated with poor outcome.
KeywordsBreast Cancer Overall Survival Tissue Inhibitor Human Breast Carcinoma Intrinsic Subtype
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