Comprehensive analysis of novel three-long noncoding RNA signatures as a diagnostic and prognostic biomarkers of human triple-negative breast cancer

Abstract

Currently, traditional predictors of prognosis (tumor size, nodal status, progesterone receptor [PR], estrogen receptor [ER], or human epidermal growth factor receptor-2 [HER2]) are insufficient for precise survival prediction for triple-negative breast cancer (TNBC). Long noncoding RNAs (lncRNAs) have been observed to exert critical functions in cancer, including in TNBC. Nevertheless, systematically tracking expression-based lncRNA biomarkers based on the sequence data for the prediction of prognosis in TNBC has not yet been investigated. To ascertain whether biomarkers exist that can distinguish TNBC from adjacent normal tissue or nTNBC, we implemented a comprehensive analysis of lncRNA expression profiles and clinical data of 1097 BC samples from The Cancer Genome Atlas database. A total of 1510 differentially expressed lncRNAs in normal and TNBC samples were extracted. Similarly, 672 differentially expressed lncRNAs between nTNBC and TNBC samples were detected. The receiver operating characteristic curve analysis indicated that three upregulated lncRNAs (AC091043.1, AP000924.1, and FOXCUT) may be of strong diagnostic value for predicting the existence of TNBC in the training and validation sets (area under the curve (AUC > 0.85). Kaplan-Meier analysis demonstrated that the other three lncRNAs (AC010343.3, AL354793.1, and FGF10-AS1) were associated with the prognosis of TNBC patients (P < 0.05). We used the three overall survival (OS)-related lncRNAs to establish a three-lncRNA signature. Multivariate Cox regression analysis suggested that the three-lncRNA signature was a prognostic factor independent of other clinical variables ( P < 0.01) for predicting OS in TNBC patients that could be utilized to classify patients into high- or low-risk subgroups. Our results might provide efficient signatures for clinical diagnosis and prognostic evaluation of TNBC.

Keywords: diagnosis; long noncoding RNAs; prognosis; signature; triple-negative breast cancer.