Development and validation of a novel 15-CpG-based signature for predicting prognosis in triple-negative breast...

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.