Gene Set: STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN

Standard name STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN
Systematic name M10880
Brief description Down-regulated genes classifying non-tumor lung tissues by age after incution of lung cancer by urethane injection [PubChem=5641]: early (24-26 weeks) vs late (46 weeks).
Full description or abstract One area of intensive investigation is to understand complex cellular and signaling interactions in the tumor microenvironment. Using a novel, although straightforward, microarray approach, we defined a gene expression signature from the lung tumor microenvironment in the murine A/J-urethane model of human lung adenocarcinoma. The tumor microenvironment is reflected by the composition of the cell types present and alterations in mRNA levels, resulting in a Field Effect around the tumor. The genes composing the Field Effect expression signature include proteases and their inhibitors, inflammation markers, and immune signaling molecules. By several criteria, the Field Effect expression signature can be attributed to the macrophage lineage, suggesting a qualitative change in the expression pattern of tumor-associated macrophages (TAM) observed in lung tumors. The protein expression levels for a number of Field Effect genes were verified by Western blot analysis of lung homogenates, and for their expression in macrophages and parenchymal cells outside of the tumors by immunohistochemistry. In addition, the Field Effect expression signature was used to classify bronchoalveolar lavage (BAL) cells from tumor-bearing or age-matched control mice. Using a variety of statistical measures, the Field Effect expression signature correctly classified the BAL cells >94% of the time. Finally, the protein levels for several Field Effect genes were higher in cell-free BAL fluid, indicating they may be secreted by the TAMs. This work suggests that TAMs generate a unique gene expression signature within the tumor microenvironment, and this signature could potentially be used for identifying lung cancer from BAL cells and/or fluid.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18172294   Authors: Stearman RS,Dwyer-Nield L,Grady MC,Malkinson AM,Geraci MW
Exact source Table 1S: AGE
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(show 4 gene sets from the same authors)
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_MG_U74
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Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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