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首页> 外文期刊>Genomics >The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: An illustration
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The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: An illustration

机译：5-氟尿嘧啶/亚叶酸钙化学疗法对CpG甲基化的影响或白细胞异质性的混杂作用：一个例证

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摘要

Blood-based epigenome-wide association studies that aim at comparing CpG methylation between colorectal cancer (CRC) patients and controls can lead to the discovery of diagnostic or prognostic biomarkers. Numerous confounders can lead to spurious associations. We aimed to see if 5-fluorouracil (5-FU)/leucovorin chemotherapy administered to cases prior to the collection of their blood has an effect on methylation. 304 patients who received treatment and 273 who did not were profiled on the HumanMethylation450 array. Association tests were adjusted for confounders, including proxies for leukocyte cell counts. There were substantial methylation differences between these two groups that vanished once the leukocyte heterogeneity was accounted for. We observed a significant decrease of T cells in the treatment group (CD4+: p = 10(-6); CD8+: p = 0.036) and significant increase of NK cells (p = 0.05) and monocytes (p = 0.0006). 5-FU/leucovorin has no effect on global and local blood-based methylation profiles, other than through differences in the leukocyte compositions that the treatment induced. (C) 2015 Elsevier Inc. All rights reserved.
机译：基于血液的表观基因组范围的关联研究旨在比较结直肠癌（CRC）患者和对照之间的CpG甲基化，可以发现诊断或预后的生物标志物。许多混杂因素会导致虚假的联想。我们旨在观察在血液采集之前对患者进行的5-氟尿嘧啶（5-FU）/亚叶酸胆碱化疗是否对甲基化有影响。在HumanMethylation450阵列上分析了304位接受治疗的患者和273位未接受治疗的患者。针对混杂因素（包括白细胞计数代理）调整了关联测试。一旦考虑了白细胞异质性，这两组之间的甲基化差异就很大。我们观察到治疗组中T细胞显着减少（CD4 +：p = 10（-6）; CD8 +：p = 0.036），NK细胞（p = 0.05）和单核细胞（p = 0.0006）显着增加。 5-FU /亚叶酸钙对整体和局部基于血液的甲基化谱图没有影响，除了通过治疗诱导的白细胞组成的差异。 （C）2015 Elsevier Inc.保留所有权利。

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