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| Status |
Public on Oct 06, 2009 |
| Title |
GEMINI (Gastric Encyclopedia of Molecular Interactions and Nodes for Intervention) Phases A-C |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Genome-wide mRNA expression profiles of 25 unique gastric cancer cell lines (GCCLs). Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 25 unique GCCLs, and in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups.
Keywords: gastric cancer, cell culture
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| Overall design |
Profiling of 25 unique Gastric Cancer Cell Lines on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Replicates are included for a total of 33 arrays.
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| Contributor(s) |
Ooi C, Tan P |
| Citation(s) |
19798449, 30115935 |
| |
| Submission date |
Mar 30, 2009 |
| Last update date |
May 21, 2019 |
| Contact name |
Chia-Huey Ooi |
| Organization name |
F. Hoffmann-La Roche Ltd.
|
| Street address |
Grenzacherstrasse 124
|
| City |
Basel |
| ZIP/Postal code |
4070 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (33)
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| This SubSeries is part of SuperSeries: |
| GSE15460 |
Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer |
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| Relations |
| BioProject |
PRJNA122977 |
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