Analysis of pathway activity in primary tumors and NCI60 cell lines using gene expression profiling data.
To determine cancer pathway activities in nine types of primary tumors and NCI60 cell lines, we applied an in silica 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 approximately 70% of lung adenocarcinomas but inactive in most squamous cell carcinomas, pulmonary carcinoids, and small cell lung carcinomas. In contrast, the TGF-beta, TNF-alpha, Src, Myc, E2F3, and beta-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, beta-catenin, TNF-alpha, or TGF-beta 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.
Feng
Xing-Dong
XD
Integrative Biology, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Huang
Shu-Guang
SG
Shou
Jian-Yong
JY
Liao
Bi-Rong
BR
Yingling
Jonathan M
JM
Ye
Xiang
X
Lin
Xi
X
Gelbert
Lawrence M
LM
Su
Eric W
EW
Onyia
Jude E
JE
Li
Shu-Yu
SY
D045744:Cell Line, Tumor; D019295:Computational Biology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism*