Breast Cancer Molecular Signatures as Determined by SAGE: Correlation with Lymph Node Status

作者：Martı́n C. Abba, Hongxia Sun, Kathleen A. Hawkins, Jeffrey A. Drake, Yuhui Hu, Maria Ines Nunez, Sally Gaddis, Tao Shi, Steve Horvath, Ayşegül A. Şahin, C. Marcelo Aldaz · 发表于：Molecular Cancer Research · 年份：2007 · DOI：10.1158/1541-7786.mcr-07-0055 · 被引用次数：115 · 研究领域：Gene expression and cancer classification、Breast Cancer Treatment Studies、Molecular Biology Techniques and Applications

Global gene expression measured by DNA microarray platforms have been extensively used to classify breast carcinomas correlating with clinical characteristics, including outcome. We generated a breast cancer Serial Analysis of Gene Expression (SAGE) high-resolution database of approximately 2.7 million tags to perform unsupervised statistical analyses to obtain the molecular classification of breast-invasive ductal carcinomas in correlation with clinicopathologic features. Unsupervised statistical analysis by means of a random forest approach identified two main clusters of breast carcinomas, which differed in their lymph node status (P=0.01); this suggested that lymph node status leads to globally distinct expression profiles. A total of 245 (55 up-modulated and 190 down-modulated) transcripts were differentially expressed between lymph node (+) and lymph node (-) primary breast tumors (fold change, >or=2; P<0.05). Various lymph node (+) up-modulated transcripts were validated in independent sets of human breast tumors by means of real-time reverse transcription-PCR (RT-PCR). We validated significant overexpression of transcripts for HOXC10 (P=0.001), TPD52L1 (P=0.007), ZFP36L1 (P=0.011), PLINP1 (P=0.013), DCTN3 (P=0.025), DEK (P=0.031), and CSNK1D (P=0.04) in lymph node (+) breast carcinomas. Moreover, the DCTN3 (P=0.022) and RHBDD2 (P=0.002) transcripts were confirmed to be overexpressed in tumors that recurred within 6 years of follow-up by real-time RT-PCR. In addition, ...