Analysis of Pathway Activity in Primary Tumors and NCI60 Cell Lines Using Gene Expression Profiling Data

作     者：Xing-Dong Feng Shu-Guang Huang Jian-Yong Shou Bi-Rong Liao Jonathan M. Yingling Xiang Ye Xi Lin Lawrence M. Gelbert Eric W. Su Jude E. Onyia Shu-Yu Li 

作者机构：Integrative BiologyLilly Research Laboratories Eli Lilly and Company Lilly Corporate Center Indianapolis IN 46285 USA Global Discovery ＆ Development StatisticsLilly Research Laboratories Eli Lilly and Company Lilly Corporate Center Indianapolis IN 46285 USA Cancer Discovery Research Lilly Research Laboratories Eli Lilly and Company Lilly Corporate Center Indianapolis IN 46285 USA 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2007年第5卷第1期

页      面：15-24页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：cancer pathways gene expression profiling supervised learning classification 

摘      要：To determine cancer pathway activities in nine types of primary tumors and NCI60 cell lines, we applied an in silico approach by examining gene signatures reflective of consequent pathway activation using gene expression data. Supervised learning approaches predicted that the Ras pathway is active in -70% of lung adenocarcinomas but inactive in most squamous cell carcinomas, pulmonary carcinoids, and small cell lung carcinomas. In contrast, the TGF-β, TNF-α, Src, Myc, E2F3, and β-catenin pathways are inactive in lung adenocarcinomas. We predicted an active Ras, Myc, Src, and/or E2F3 pathway in significant percentages of breast cancer, colorectal carcinoma, and gliomas. Our results also suggest that Ras may be the most prevailing oncogenic pathway. Additionally, many NCI60 cell lines exhibited a gene signature indicative of an active Ras, Myc, and/or Src, but not E2F3, β-catenin, TNF-α, or TGF-β pathway. To our knowledge, this is the first comprehensive survey of cancer pathway activities in nine major tumor types and the most widely used NCI60 cell lines. The ＂gene expression pathway signatures＂ we have defined could facilitate the understanding of molecular mechanisms in cancer development and provide guidance to the selection of appropriate cell lines for cancer research and pharmaceutical compound screening.