Identification of a Six-lncRNA Signature With Prognostic Value for Breast Cancer Patients

Abstract

Breast cancer (BRCA) is the most common cancer and a major cause of death in women. Long non-coding RNAs (lncRNAs) are emerging as key regulators and have been implicated in carcinogenesis and prognosis. In this study, we aimed to develop a lncRNA signature of BRCA patients to improve risk stratification. In the training cohort (GSE21653, n = 232), 17 lncRNAs were identified by univariate Cox proportional hazards regression, which were significantly associated with patients' survival. The least absolute shrinkage and selection operator-penalized Cox proportional hazards regression analysis was used to identify a six-lncRNA signature. According to the median of the signature risk score, patients were divided into a high-risk group and a low-risk group with significant disease-free survival differences in the training cohort. A similar phenomenon was observed in validation cohorts (GSE42568, n = 101; GSE20711, n = 87). The six-lncRNA signature remained as independent prognostic factors after adjusting for clinical factors in these two cohorts. Furthermore, this signature significantly predicted the survival of grade III patients and estrogen receptor-positive patients. Furthermore, in another cohort (GSE19615, n = 115), the low-risk patients that were treated with tamoxifen therapy had longer disease-free survival than those who underwent no therapy. Overall, the six-lncRNA signature can be a potential prognostic tool used to predict disease-free survival of patients and to predict the benefits of tamoxifen treatment in BRCA, which will be helpful in guiding individualized treatments for BRCA patients.

Keywords: breast cancer; disease-free survival; long non-coding RNA; prognosis; signature.