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Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target

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Technical Report,05 May 2015,04 May 2016

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Cedars-Sinai Medical Center Los Angeles United States

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We identified a tumor microenvironment-based activated fibroblast gene signature that correlates with poor survival in ovarian cancer patients. We are refining this gene signature to develop biomarkers for the identification of patients with adverse outcomes on standard treatment. In the first part of this project, we have analyzed a gene signature for the identification of patients who are unlikely to benefit from standard surgery andor chemotherapy and should be considered for clinical trials targeting specific pathways in the tumor microenvironment. Specifically, we found that suboptimal surgical outcome is associated with a molecularly aggressive subtype of ovarian cancer characterized by the presence of activated fibroblasts, which likely contributes to chemotherapy resistance. In the current part of the project, we focused on the molecular characterization of activated cancer fibroblasts. First, we defined COL11A1 as a highly specific biomarker of activated fibroblasts. Second, using COL11A1 as a seed to identify coexpressed genes, we demonstrated that activated fibroblasts express a highly conserved gene signature across genetically different epithelial cancer types. In the last part of the project no-cost extension, we will validate the gene signature in patient samples and develop a preliminary quantitative assay for use in the clinical setting.

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