Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers.
Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers.
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DOI：
10.18632/oncotarget.1782
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发表时间：
2014-02-15
期刊：
影响因子：
--
通讯作者：
Ahuja N
中科院分区：
文献类型：
--
作者：
Li H;Chiappinelli KB;Guzzetta AA;Easwaran H;Yen RW;Vatapalli R;Topper MJ;Luo J;Connolly RM;Azad NS;Stearns V;Pardoll DM;Davidson N;Jones PA;Slamon DJ;Baylin SB;Zahnow CA;Ahuja N
表观遗传疗法正在成为一种潜在的实体瘤治疗方法。为了研究其作用机制，我们对63种癌症细胞系（乳腺癌、结直肠癌和卵巢癌）进行了DNA甲基转移酶抑制剂5-阿扎胞苷（AZA）治疗后的整合表达和甲基化分析。基因集富集分析显示，在所有三种癌症（14.4-31.3%）中，包括干扰素信号、抗原加工和呈递、细胞因子/趋化因子在内的免疫调节途径显著富集。睾丸癌抗原的强烈上调也被观察到。在TCGA和GEO的肿瘤表达数据中，由这些免疫调节通路基因结合而成的AZA免疫基因集（AIMs）将所有三种类型的原发性肿瘤分为“高”和“低”AIM基因表达亚群。选择的患者活检样本显示，在接受表观遗传治疗后，AIM基因上调。这些结果表明，DNA去甲基化药物在多种癌症中具有广泛的免疫刺激作用。
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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DOI：
10.1158/1541-7786.mcr-11-0520
发表时间：
2012-03
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Chiappinelli KB;Haynes BC;Brent MR;Goodfellow PJ
通讯作者：
Goodfellow PJ
影响因子：
14.9
作者：
Almeida LG;Sakabe NJ;deOliveira AR;Silva MC;Mundstein AS;Cohen T;Chen YT;Chua R;Gurung S;Gnjatic S;Jungbluth AA;Caballero OL;Bairoch A;Kiesler E;White SL;Simpson AJ;Old LJ;Camargo AA;Vasconcelos AT
通讯作者：
Vasconcelos AT
影响因子：
7
作者：
Easwaran, Hariharan;Johnstone, Sarah E.;Baylin, Stephen B.
通讯作者：
Baylin, Stephen B.
通过 DNA 低甲基化和环 AMP 增加前列腺癌中雄激素受体共调节因子 MAGE-11 的表达。
影响因子：
5.2
作者：
Karpf, Adam R.;Bai, Suxia;James, Smitha R.;Mohler, James L.;Wilson, Elizabeth M.
通讯作者：
Wilson, Elizabeth M.
影响因子：
3.7
作者：
James, Smitha R.;Cedeno, Carlos D.;Karpf, Adam R.
通讯作者：
Karpf, Adam R.