Project description:Increasing success is being achieved in the treatment of malignancies with stromal-targeted therapies, predominantly in anti-angiogenesis and immunotherapy, predominantly checkpoint inhibitors. Despite 15 years of clinical trials with anti-VEGF pathway inhibitors for cancer, we still find ourselves lacking reliable predictive biomarkers to select patients for anti-angiogenesis therapy. For the more recent immunotherapy agents, there are many approaches for patient selection under investigation. Notably, the predictive power of an Ad-VEGF-A164 mouse model to drive a stromal response with similarities to a wound healing response shows relevance for human cancer and was used to generate stromal signatures. We have developed gene signatures for 3 stromal states and leveraged the data from multiple large cohort bioinformatics studies of gastric cancer (TCGA, ACRG) to further understand how these relate to the dominant patient phenotypes identified by previous bioinformatics efforts. We have also designed multiplexed IHC assays that robustly represent the vascular and immune diversity in gastric cancer. Finally, we have used this methodology to arrive at a hypothesis of how angiogenesis and immunotherapy may fit into the experimental approaches for gastric cancer treatments. The Ad-VEGF-A164 flank model was performed as described in Flank tissue from harvest day 0, day 5, day 20, and day 60 was taken for RNA generation. Samples for messenger RNA (mRNA) profiling studies were processed by Asuragen, Inc. (Austin, TX, USA) using GeneChipÂ® Mouse Genome 430 2.0 Array (Affymetrix, Santa Clara, CA) according to the company's standard operating procedures as described previously in detail [45]. A summary of the image signal data, detection calls and gene annotations for every gene interrogated on the arrays was generated using the Affymetrix Statistical Algorithm MAS 5.0 (GCOS v1.3) algorithm (scaling factor = 1500).

2016-01-07 | E-GEOD-76588 | biostudies-arrayexpress

Genomic profiling of gastric carcinoma in situ and gastric adenomas by array-based comparative genomic hybridization

Project description:This SuperSeries is composed of the following subset Series: GSE19566: Genomic profiling of gastric carcinoma in situ by array-based comparative genomic hybridization GSE19574: Genomic profiling of gastric adenomas by array-based comparative genomic hybridization Refer to individual Series

2010-01-31 | E-GEOD-19575 | biostudies-arrayexpress

Stromal myofibroblasts drive tumorigenesis in Peutz-Jeghers Syndrome polyposis models

Project description:Germline mutations in LKB1 predispose to hereditary Peutz-Jeghers Syndrome (PJS), manifesting with gastrointestinal polyposis. We discovered that conditional deletion of Lkb1 in stromal fibroblasts using Fsp1-Cre leads to expansion of stromal cells and gastrointestinal polyposis in mice. Here we have investigated gene expression signatures in the Fsp1-Cre;Lkb1fl/fl mouse polyps harbouring bi-allelic deletion of Lkb1 in stromal cells together with wild-type epithelium. We provide RNA-seq gene expression data of 6 polyps, 4 adjacent gastric mucosa samples and 5 wild-type gastric mucosa samples from littermate controls. Our experiment demonstrates e.g. activated cytokine signaling and inflammatory pathways in the polyps.

2018-01-05 | E-MTAB-5549 | biostudies-arrayexpress

A signature predicting poor prognosis in gastric and ovarian cancer represents a coordinated macrophage and stromal-response.

Project description:Genome wide mRNA expression profiling of 94 gastric tumours derived from Australian based cohort was performed. . From this data we identified a cluster of co-expressed genes termed the stromal response cluster which almost perfectly differentiates tumor from its non-malignant gastric tissue and hence can be regarded as a highly tumor-specific gene expression signature. We show that these genes are consistently co-expressed across a range of independent gastric datasets as well as other cancer types suggesting a conserved functional role in cancer. Profiling of 94 primary gastric tumors on Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays. All tumors were collected with approvals from Peter MacCallum Cancer Center, Australia; the Research Ethics Review Committee; and signed informed patient consent.

2014-04-01 | E-GEOD-51105 | biostudies-arrayexpress