接受细胞毒性化疗可能会改变乳腺癌患者的 DNA 甲基化 (DNAm)。我们使用 Illumina MmethylationEPIC 阵列对 125 名乳腺癌患者在化疗前后抽取的血液进行了 DNAm 分析。使用针对单核细胞比例调整的线性回归模型评估了 588,798 个单独的 CpG（包括 41,207 个启动子区域）的 DNAm 变化。进行基因集富集分析（GSEA）来识别与化疗相关的关键基因本体论（GO）生物过程或京都基因和基因组百科全书（KEGG）途径。结果在接受化疗 (n = 1273) 和未接受化疗 (n = 872) 的乳腺癌患者（1808 份血液，337 份唾液）的单独队列中得到验证。总共 141 个差异甲基化 CpG 和 11 个启动子显着相关在配对样本和单时间点分析中进行多次测试校正后进行化疗。启动子区域的 GSEA（通过测试统计预先排序）确定了与感官知觉和化学刺激检测相关的六个受抑制的生物过程 (p < 4.67e-8)，包括嗅觉知觉 (GO:0007606、GO:0007608、GO:0009593 ，GO：0050906，GO：0050907，GO：0050911）。在验证数据集中，相同的六个生物过程被显着抑制（p < 9.02e-14）。 KEGG 通路嗅觉转导 (hsa04740) 也被显着抑制（配对样本 = 1.72e-9、单时间点血液 = 2.03e-15 和单时间点唾液 = 7.52e-56）。生物过程和途径中印记基因的研究表明化疗可能影响嗅觉的生物机制。© 2023。作者。

Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients.We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva).A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e-8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e-14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (ppaired-samples = 1.72e-9, psingle-timepoint-blood = 2.03e-15 and psingle-timepoint-saliva = 7.52e-56).The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.© 2023. The Author(s).