Expression analysis of NF-κB interacting long noncoding RNAs in breast cancer

The nuclear factor-κB (NF-κB) has a prominent role in development of breast cancer and response of patients to conventional therapies. Several factors regulate the activity of this transcription factor. In the current investigation, we compared expression levels of five long non-coding RNAs (lncRNAs) with putative interactions with NF-κB namely CHAST, ADINR, DICER1-AS1, HNF1A-AS1 and NKILA between 78 breast cancer tissues and their paired adjacent non-cancerous tissues (ANCTs). We also assessed expression levels of ATG5 and CEBPA mRNA coding genes that are functionally linked with NF-κB signaling in these two sets of samples. All assessed genes except for NKILA were significantly down-regulated in tumoral tissues compared with ANCTs. Expression of NKILA was not significantly different between tumoral tissues and ANCTs. Expression levels of CEBPA and HNF1A-AS were significantly associated with cancer stage (P values of 0.03 and 0.02 respectively). Expression levels of ATG5 tended to be associated with mitotic rate (P = .05). The association between expression levels of ATG5 and tumor size was also significant (P = .02). Expression of CHAST was significantly associated with PR status (P = .04) and tended to be associated with ER status (P = .05). Finally, expression of NKILA was significantly associated with first pregnancy age (P = .01). No other significant association was detected between expression levels of assessed genes and clinical parameters. Expression levels of mentioned genes were significantly correlated with each other. The most significant correlations were found between CHAST and ADINR (correlation coefficients of 0.78 and 0.69 in tumoral tissues and ANCTs respectively). Based on the area under curve (AUC) values, DICER1-AS and CEBPA had the best performance in differentiation of tumoral tissues from ANCTs (AUC values of 0.92 and 0.90 respectively. Combination of transcript quantities of six genes could differentiate these two sets of samples with 92.3% sensitivity, 91% specificity and diagnostic power of 95%. The current project highlights dysregulation of NF-κB-associated genes in breast cancer tissues and suggests them as potential diagnostic markers in breast cancer.