Gene Set: BORCZUK_MALIGNANT_MESOTHELIOMA_DN

Standard name BORCZUK_MALIGNANT_MESOTHELIOMA_DN
Systematic name M7988
Brief description Genes down-regulated in biphasic (mixed) vs epithelial subtypes of malignant peritoneal mesothelioma.
Full description or abstract Malignant mesothelioma is an aggressive neoplastic proliferation derived from cells lining serosal membranes. The biological and clinical characteristics of epithelial type malignant mesothelioma are distinct from those of biphasic and sarcomatous type tumors. The goal of our study was to examine the molecular basis for this distinction. Microarray analysis confirmed that the molecular signatures of epithelial and biphasic histologic subtypes were distinct. Among the differentially expressed functional gene categories was the ubiquitin-proteasome pathway, which was upregulated in biphasic tumors. Cytotoxicity experiments indicated that 211H cells derived from biphasic tumors were synergistically sensitive to sequential combination regimens containing the proteasome inhibitor bortezomib and oxaliplatin. The mechanism of this synergistic response, which was not detected in cells of epithelial tumor origin, was apoptosis. Together, our results identify the ubiquitin-proteasome pathway as a biomarker of poor prognosis biphasic peritoneal mesothelioma tumors and suggest that proteasome inhibitors could increase the effectiveness of cytotoxic chemotherapy in this subset of patients.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16862182   Authors: Borczuk AC,Cappellini GC,Kim HK,Hesdorffer M,Taub RN,Powell CA
Exact source Table 1S
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_HG_U95
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Version history 3.0: First introduced

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