Long Noncoding RNAs (lncRNAs) as Biomarkers of Prognosis in TNBC and Non-TNBC Breast Cancer Patients

Abstract

Functional studies have shown that long noncoding RNAs (lncRNAs) play different roles in gene expression regulation, acting as epigenetic factors. Accumulating evidence indicates that lncRNAs modulate diverse biological processes, and their altered expression is associated with the development and progression of cancer, including BC. Here, aiming to identify lncRNAs associated with breast cancer, we performed a re-analysis of the expression data from 1071 tumors of eligible patients in the LACRN-MPBC Study. Using normalized data, we compared the expression profiles of triple-negative breast cancer (TNBC; 170 cases) and a heterogeneous group of non-TNBC tumors (782 cases). A total of 59 differentially expressed lncRNAs (DELncRNAs) could be identified based on the criteria of |log2FC| ≥ 1 and FDR < 0.05, using the DESeq2 R package. In the Kaplan–Meier survival analysis, we identified DELncRNAs that affect disease-free survival and/or overall survival, with eight of them in TNBC and 27 in non-TNBC patients. Multivariate Cox proportional-hazards models were used to evaluate independent predictors of survival. Two DELncRNAs, VLDLR-AS1 and PART1, were identified as independent prognostic markers for TNBC patients, while seven (LINC00239, FAM30A, LINC00842, LINC01315, EGOT, LY6E-DT, and SLC25A21-AS1) were independent prognostic markers for non-TNBC patients. Our computational study identifies several candidate lncRNAs associated with clinical outcomes in breast cancer. However, the DELncRNAs identified here should be interpreted as preliminary candidates, which require future validation and functional studies to determine their biological roles and evaluate their potential as prognostic biomarkers.