Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE57343 | GEO | 2014/05/08
SECONDARY ACCESSION(S): PRJNA246409
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
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Project description:Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA). Gene Set Enrichment Analysis demonstrated significant enrichment for immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon signaling, antigen processing and presentation, and cytokines/chemokines. Strong upregulation of cancer testis antigens was also observed. An AZA IMmune gene set (AIMs) derived from the union of these immunomodulatory pathway genes classified primary tumors from all three types, into "high" and "low" AIM gene expression subsets in tumor expression data from both TCGA and GEO. Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-05-08 | E-GEOD-57343 | biostudies-arrayexpress
Project description:Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA). Gene Set Enrichment Analysis demonstrated significant enrichment for immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon signaling, antigen processing and presentation, and cytokines/chemokines. Strong upregulation of cancer testis antigens was also observed. An AZA IMmune gene set (AIMs) derived from the union of these immunomodulatory pathway genes classified primary tumors from all three types, into “high” and “low” AIM gene expression subsets in tumor expression data from both TCGA and GEO (GSE42284, GSE10893, and GSE26712 for the colon, breast, and ovarian samples, respectively). Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers. A total of 338 samples were analyzed.
2014-05-08 | E-GEOD-57342 | biostudies-arrayexpress
Project description:Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA). Gene Set Enrichment Analysis demonstrated significant enrichment for immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon signaling, antigen processing and presentation, and cytokines/chemokines. Strong upregulation of cancer testis antigens was also observed. An AZA IMmune gene set (AIMs) derived from the union of these immunomodulatory pathway genes classified primary tumors from all three types, into “high” and “low” AIM gene expression subsets in tumor expression data from both TCGA and GEO (GSE42284, GSE10893, and GSE26712 for the colon, breast, and ovarian samples, respectively). Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers.
2014-05-08 | GSE57342 | GEO
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