Project description:This SuperSeries is composed of the following subset Series:; GSE15455: GEMINI (Gastric Encyclopedia of Molecular Interactions and Nodes for Intervention) Phases A-C; GSE15456: Primary Gastric Cancer Expression Profiles (UK Patient Cohort); GSE15459: Gastric Cancer Project '08 (Singapore Patient Cohort); GSE15537: GEMINI (Gastric Encyclopedia of Molecular Interactions and Nodes for Intervention) Phases A-C, normal skin fibroblasts Experiment Overall Design: Refer to individual Series
Project description:Genome-wide mRNA expression profiles of 70 primary gastric tumors from the Australian patient cohort. Like many cancers, gastric adenocarcinomas (gastric cancers) show considerable heterogeneity between patients. Thus, there is intense interest in using gene expression profiles to discover subtypes of gastric cancers with particular biological properties or therapeutic vulnerabilities. Identification of such subtypes could generate insights into the mechanisms of cancer progression or lay the foundation for personalized treatments. Here we report a robust gene-xpression-based clustering of a large collection of gastric adenocarcinomas from Singaporean patients [GSE34942 and GSE15459]. We developed and validated a classifier for the three subtypes in Australian patient cohort. Profiling of 70 primary gastric tumors on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. All tumors were collected with approvals from Peter MacCallum Cancer Center, Australia; the Research Ethics Review Committee; and signed patient informed consent.
Project description:Genome-wide mRNA expression profiles of 70 primary gastric tumors from the Australian patient cohort. Like many cancers, gastric adenocarcinomas (gastric cancers) show considerable heterogeneity between patients. Thus, there is intense interest in using gene expression profiles to discover subtypes of gastric cancers with particular biological properties or therapeutic vulnerabilities. Identification of such subtypes could generate insights into the mechanisms of cancer progression or lay the foundation for personalized treatments. Here we report a robust gene-xpression-based clustering of a large collection of gastric adenocarcinomas from Singaporean patients [GSE34942 and GSE15459]. We developed and validated a classifier for the three subtypes in Australian patient cohort.
Project description:Genome-wide mRNA expression profiles of 56 primary gastric tumors from the Singapore patient cohort, batch B. Like many cancers, gastric adenocarcinomas (gastric cancers) show considerable heterogeneity between patients. Thus, there is intense interest in using gene expression profiles to discover subtypes of gastric cancers with particular biological properties or therapeutic vulnerabilities. Identification of such subtypes could generate insights into the mechanisms of cancer progression or lay the foundation for personalized treatments. Here we report a robust gene-expression-based clustering of a large collection of gastric adenocarcinomas (with GSE15459) from Singaporean patients. Profiling of 56 primary gastric tumors on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. All tumors were collected with approvals from the National Cancer Centre, Singapore; the Research Ethics Review Committee; and signed patient informed consent.
Project description:Genome-wide mRNA expression profiles of 31 primary gastric tumors from the UK patient cohort. 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 GC cell lines, 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