...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>EBioMedicine >DNA methylation of indoleamine 2,3-dioxygenase 1 (IDO1) in head and neck squamous cell carcinomas correlates with IDO1 expression, HPV status, patients’ survival, immune cell infiltrates, mutational load, and interferon γ signature
【24h】

DNA methylation of indoleamine 2,3-dioxygenase 1 (IDO1) in head and neck squamous cell carcinomas correlates with IDO1 expression, HPV status, patients’ survival, immune cell infiltrates, mutational load, and interferon γ signature

机译：头颈部鳞状细胞癌中吲哚胺2,3-二加氧酶1（IDO1）的DNA甲基化与IDO1表达，HPV状况，患者存活，免疫细胞浸润，突变负荷和干扰素γ信号相关

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background The immune checkpoint, indoleamine 2,3-dioxygenase 1, is under investigation as target of novel immunotherapies for cancers, including head and neck squamous cell carcinomas (HNSCC). The aim of our study was to analyze DNA methylation of the encoding gene ( IDO1 ) in HNSCC. Methods Methylation of three CpG sites within the promoter, promoter flank, and gene body was investigated and correlated with mRNA expression, immune cell infiltration, mutational burden, human papillomavirus (HPV)-status, and overall survival in a cohort of N ?=?528 HNSCC patients obtained from The Cancer Genome Atlas. In addition, IDO1 immunohistochemistry and DNA methylation analysis was performed in an independent cohort of N ?=?138 HNSCC samples. Findings Significant inverse correlations of IDO1 methylation and IDO1 mRNA expression were found in the promoter and promoter flank region (Spearman's ρ ?=??0.163 and ρ ?=??0.377, respectively) while a positive correlation was present in the gene body ( ρ ?=?0.502; all P ??0.001). IDO1 DNA methylation significantly correlated with IDO1 protein expressing immune cells as well as tumor cells. IDO1 promoter flank hypermethylation was significantly associated with poor overall survival ( P ??0.001). In addition, we discovered significant correlations between IDO1 methylation and expression with RNA signatures of immune cell infiltrates and with HPV-status, mutational load (methylation only), and interferon γ signature. Interpretation Our results suggest IDO1 expression levels are epigenetically regulated by DNA methylation. This study provides rationale to test IDO1 methylation as potential biomarker for prediction of response to IDO1 immune checkpoint inhibitors in HNSCC.
机译：背景技术免疫检查点，吲哚胺2，3-二加氧酶1，正在研究作为新型免疫疗法的靶标，包括头颈部鳞状细胞癌（HNSCC）。我们研究的目的是分析HNSCC中编码基因（IDO1）的DNA甲基化。方法研究启动子，启动子侧翼和基因体中三个CpG位点的甲基化，并与mRNA表达，免疫细胞浸润，突变负荷，人乳头瘤病毒（HPV）状态和N ==？从癌症基因组图谱中获得了528例HNSCC患者。另外，在N≥＝ 138个HNSCC样品的独立队列中进行IDO1免疫组织化学和DNA甲基化分析。发现在启动子和启动子侧翼区域（分别为Spearman'sρ？=？0.163和ρ？==？0.377）发现IDO1甲基化和IDO1 mRNA表达有显着的负相关，而在基因体中却存在正相关（ρ λ＝ 0.502;所有P≤0.001。 IDO1 DNA甲基化与表达IDO1蛋白的免疫细胞以及肿瘤细胞显着相关。 IDO1启动子的侧翼高甲基化与总生存期差有关（P≤0.001）。此外，我们发现IDO1甲基化和表达与免疫细胞浸润的RNA标记以及HPV状态，突变负荷（仅甲基化）和干扰素γ标记之间存在显着相关性。解释我们的结果表明IDO1表达水平受DNA甲基化表观遗传调控。这项研究为测试IDO1甲基化作为预测HNSCC对IDO1免疫检查点抑制剂反应的潜在生物标志物提供了理论依据。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号