Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
J Cell Mol Med. 2020 Aug;24(16):9378-9387. doi: 10.1111/jcmm.15588. Epub 2020 Jul 10.
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.
DNA 甲基化是一种重要的生物学调控机制，它可以改变基因表达而不改变 DNA 序列。越来越多的研究表明，DNA 甲基化数据在肿瘤学领域中起着至关重要的作用。然而，三阴性乳腺癌 (TNBC) 中的甲基化位点特征尚不清楚。在我们的研究中，我们分析了三个阶段来自癌症基因组图谱 (TCGA) 的 158 个 TNBC 样本和 98 个非癌样本。在发现阶段，通过单变量 Cox 比例风险回归 (CPHR) 分析鉴定了 86 个 CpG，这些 CpG 与总生存期显著相关（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算子 (LASSO) Cox 回归，进一步将这些候选 CpG 缩小到基于 15 个 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了基于 15 个 CpG 的特征。此外，基于 CpG 的特征和 TNM 分期的列线图用于预测原发性集的 1、3 和 5 年总生存期，并且在三个验证集中表现出优异的性能（一致性指数：0.924、0.974 和 0.637）。这项研究表明，我们的列线图对 TNBC 的预后具有精确的预测效果，并且有可能用于临床治疗和诊断。
