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 37 unique gastric cancer cell lines (GCCLs). Keywords: gastric cancer, cell culture Profiling of 37 unique Gastric Cancer Cell Lines on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. A total of 37 arrays. 21 of these Samples represent a re-analysis of CEL files initially submitted under Series GSE15455.
Project description:Most gastric cancer (GC) patients with early stage often have no lymph node (LN) metastases, while LN metastases appear in the advanced stage. However, there are some patients who present with early stage LN metastases and no LN metastases in the advanced stage. To explore the deeper molecular mechanisms involved, we collected clinical samples from early and advanced stage GC with and without LN metastases, as well as metastatic lymph nodes. Herein, we identified a keytarget, HOXA11, that was upregulated in GC tissues and closely associated with lymphatic metastases. HOXA11 transcriptionally regulates TGFβ1 expression and activates the TGFβ1/Smad2 pathway, which in turn promotes the development of EMT. In addition, enhanced Smad2 expression promotes the secretion of VEGF-C, which in turn induces lymphangiogenesis. These findings provide a plausible mechanism forHOXA11-modulated tumor in lymphatic metastasis and suggest thatHOXA11 may represent a potential therapeutic target for clinical intervention in LN-metastatic gastric cancer.
Project description:Establishment and molecular characterization of 49 peritoneally-metastatic gastric cancer cell lines from 18 patients’ ascites. We performed comprehensive transcriptome analyses using microarrays of our established gastric cancer cell lines.
Project description:Molecular characterization of 7 peritoneally-metastatic gastric cancer cell lines and primary cancer cells established from a patients’ ascites. We performed comprehensive transcriptome analyses using microarrays of our established gastric cancer cell lines and primary cancer cells.
Project description: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 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.
