Identification of long non-coding RNA-mediated transcriptional dysregulation triplets reveals global patterns and prognostic biomarkers for ER(+)/PR(+), HER2(−) and triple negative breast cancer

Breast cancer (BRCA) is the most common type of cancer in adult females. Estrogen receptor (ER)(+)/progesterone receptor (PR)(+), human epidermal-growth factor receptor 2 (HER2)(−) BRCA and triple-negative breast cancer (TNBC) are two important subtypes of this disease. Long non-coding RNA (lncRNA)-mediated transcriptional dysregulation triplets (lncTDTs) may contribute to the development of cancer; however, the precise functional roles of lncTDTs in ER(+)/PR(+), HER2(−) BRCA and TNBC require further investigation. In the present study, an integrated and computational approach was conducted to identify lncTDTs based on transcription factor (TF), gene, lncRNA expression profiles and experimentally verified TF-gene interactions. The regulatory patterns of these lncTDTs are complex and differed in ER(+)/PR(+), HER2(−) BRCA and TNBC. Of note, five common lncTDTs were reported for these BRCA subtypes. Functional analysis revealed lncTDTs to be enriched in the PI3K/AKT signaling pathway within the two BRCA subtypes. Additionally, certain lncTDTs were associated with survival and may be considered candidate prognostic biomarkers for BRCA subtypes. Collectively, the results of the present study provide novel insight into the functions and mechanisms of lncRNAs in ER(+)/PR(+), HER2(−) BRCA and TNBC, and may aid the development of targeted treatments against certain subtypes of BRCA.