a prognostic gene expression profile that predicts circulating tumor cell presence in breast cancer patients一个预测预后基因表达谱在乳腺癌患者循环肿瘤细胞存在.pdfVIP

A Prognostic Gene Expression Profile That Predicts Circulating Tumor Cell Presence in Breast Cancer Patients 1 2 3 1,2 Timothy J. Molloy , Paul Roepman , Bjørn Naume , Laura J. van’t Veer * 1 Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands, 2 Agendia BV, Amsterdam, The Netherlands, 3 Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway Abstract The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into ‘‘good prognosis’’ or ‘‘poor prognosis’’ are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the ‘‘CTC profile’’ also provided prognostic information i