Oncogenic pathway combinations predict clinical prognosis in gastric cancer

Chia Huey Ooi, Tatiana Ivanova, Jeanie Wu, Minghui Lee, Iain Beehuat Tan, Jiong Tao, Lindsay Ward, Jun Hao Koo, Veena Gopalakrishnan, Yansong Zhu, Lai Ling Cheng, Julian Lee, Sun Young Rha, Hyun Cheol Chung, Kumaresan Ganesan, Jimmy So, Khee Chee Soo, Dennis Lim, Weng Hoong Chan, Wai Keong WongDavid Bowtell, Khay Guan Yeoh, Heike Grabsch, Alex Boussioutas, Patrick Tan

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-κB, and Wnt/β-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms.

Original languageEnglish
Article numbere1000676
JournalPLoS Genetics
Volume5
Issue number10
DOIs
Publication statusPublished - 2009 Oct

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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  • Cite this

    Ooi, C. H., Ivanova, T., Wu, J., Lee, M., Tan, I. B., Tao, J., Ward, L., Koo, J. H., Gopalakrishnan, V., Zhu, Y., Cheng, L. L., Lee, J., Rha, S. Y., Chung, H. C., Ganesan, K., So, J., Soo, K. C., Lim, D., Chan, W. H., ... Tan, P. (2009). Oncogenic pathway combinations predict clinical prognosis in gastric cancer. PLoS Genetics, 5(10), [e1000676]. https://doi.org/10.1371/journal.pgen.1000676