A Five-Gene-Pair-Based Prognostic Signature for Predicting the Relapse Risk of Early Stage ER+ Breast Cancer

About 20–30% of early-stage breast cancer patients suffer relapses after surgery. To identify such high-risk patients, many signatures have been reported, but they lack robustness in data measured on different platforms. Here, we developed a signature which is robust across multiple profiling platforms, and identified reproducible omics features characterizing metastasis of estrogen receptor (ER)-positive breast cancer from the Gene Expression Omnibus database with the aid of the signature. Based on the stable within-sample relative expression orderings (REOs), we constructed a signature consisting of five gene pairs, named 5-GPS, whose REOs were significantly correlated with relapse-free survival using the univariate Cox regression model. Using 5-GPS, patients were classified into the low-risk and high-risk groups. Patients in the high-risk group have worse survival compared to those in the low-risk group using Kaplan-Meier curve analysis with the log-rank test. Applying 5-GPS to the RNA-sequencing data of stage I-IV breast cancer samples archived in The Cancer Genome Atlas (TCGA), we found that the proportion of the high-risk patients increases with the stage. The proposed REO-based signature shows potential in identifying early-stage ER+ breast cancer patients with high risk of relapse after surgery.