Additional file 14 of Candidate methylation sites associated with endocrine therapy resistance in ER+/HER2- breast cancer

Additional file 14. CpGs with concordant significant changes in the survival and resistance acquisition signatures and with significant correlation between paired DNA methylation and gene expression profiles. CpGs in single-locus (Additional File 4) and multi-locus (Additional File 7) survival signatures were selected according to three additional criteria: (i) CpG DNA methylation is significantly (adjusted p-value < 0.05) (anti-)correlated with expression of the nearby gene(s), (ii) CpG is also significantly differentially methylated (adjusted p-value < 0.05) in the corresponding RA signature at month 7 versus WT, (iii) CpG changes concordantly in survival and corresponding RA signature, that is, risk increasing loci are hypermethylated and risk decreasing loci are hypomethylated.

附加文件14：在生存特征（survival signatures）与耐药获得特征（resistance acquisition signatures）中呈现一致性显著变化，且配对DNA甲基化（DNA methylation）与基因表达谱（gene expression profiles）间存在显著相关性的CpG位点。针对单基因座（single-locus）与多基因座（multi-locus）生存特征中的CpG位点，需额外遵循以下三项筛选标准：(i) CpG位点的DNA甲基化水平与邻近基因的表达量存在显著（校正后P值（adjusted p-value）<0.05）（抗）相关性；(ii) 相较于野生型（Wild Type, WT），该CpG位点在第7个月对应的耐药获得特征中同样存在显著的差异甲基化（differentially methylated）（校正后P值<0.05）；(iii) 该CpG位点在生存特征与相应的耐药获得特征中呈现一致的变化趋势，即风险升高位点（risk increasing loci）呈高甲基化（hypermethylated），风险降低位点（risk decreasing loci）呈低甲基化（hypomethylated）。