DNA methylation is an important biological regulatory mechanism that changes gene expression without altering the DNA sequence. Increasing studies have revealed that DNA methylation data play a vital role in the field of oncology. However, the methylation site signature in triple‐negative breast cancer (TNBC) remains unknown. In our research, we analysed 158 TNBC samples and 98 noncancerous samples from The Cancer Genome Atlas (TCGA) in three phases. In the discovery phase, 86 CpGs were identified by univariate Cox proportional hazards regression (CPHR) analyses to be significantly correlated with overall survival (P  < 0.01). In the training phase, these candidate CpGs were further narrowed down to a 15‐CpG‐based signature by conducting least absolute shrinkage and selector operator (LASSO) Cox regression in the training set. In the validation phase, the 15‐CpG‐based signature was verified using two different internal sets and one external validation set. Furthermore, a nomogram comprising the CpG‐based signature and TNM stage was generated to predict the 1‐, 3‐ and 5‐year overall survival in the primary set, and it showed excellent performance in the three validation sets (concordance indexes: 0.924, 0.974 and 0.637). This study showed that our nomogram has a precise predictive effect on the prognosis of TNBC and can potentially be implemented for clinical treatment and diagnosis.

中文翻译：

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用于预测三阴性乳腺癌预后的新型基于 15-CpG 的特征的开发和验证。

DNA 甲基化是一种重要的生物调控机制，可以在不改变 DNA 序列的情况下改变基因表达。越来越多的研究表明，DNA 甲基化数据在肿瘤学领域发挥着至关重要的作用。然而，三阴性乳腺癌（TNBC）的甲基化位点特征仍然未知。在我们的研究中，我们分三个阶段分析了来自癌症基因组图谱 (TCGA) 的 158 个 TNBC 样本和 98 个非癌性样本。在发现阶段，通过单变量 Cox 比例风险回归 (CPHR) 分析确定了 86 个 CpG 与总生存期显着相关（P < 0.01)。在训练阶段，通过在训练集中进行最小绝对收缩和选择器算子 (LASSO) Cox 回归，将这些候选 CpG 进一步缩小为基于 15-CpG 的特征。在验证阶段，使用两个不同的内部集和一个外部验证集验证基于 15-CpG 的签名。此外，生成了一个包含基于 CpG 的特征和 TNM 分期的列线图来预测初级组中的 1 年、3 年和 5 年总生存率，并且在三个验证组中表现出优异的性能（一致性指数：0.924， 0.974 和 0.637）。该研究表明，我们的列线图对 TNBC 的预后具有精确的预测作用，并有可能用于临床治疗和诊断。