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

Expression analysis of NF-κB interacting long noncoding RNAs in breast cancer
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DOI:
10.1016/j.yexmp.2019.104359
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发表时间:
2020-02-01
影响因子:
3.6
通讯作者:
Taheri, Mohammad
Taheri, Mohammad
中科院分区:
医学3区
文献类型:
--
作者:
Dashti, Sepideh;Ghafouri-Fard, Soudeh;Taheri, Mohammad

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核因子-κ B(NF-κ B)在乳腺癌的发生和患者对常规治疗的反应中具有显著作用。在本研究中,我们比较了78例乳腺癌组织及其配对的相邻非癌组织(ANCT)中5种与NF-κ B相互作用的长链非编码RNA(lncRNA)的表达水平,即CHAST、ADINR、DICER 1-AS 1、HNF 1A-AS 1和NKILA。我们还评估了与NF-κ B B信号传导功能相关的ATG 5和CEBPA mRNA编码基因在这两组样本中的表达水平。NKILA在肿瘤组织和ANCT中的表达无显著差异。CEBPA和HNF 1A-AS的表达水平与肿瘤分期显著相关(P值分别为0.03和0.02)。ATG 5的表达水平倾向于与有丝分裂率相关(P = 0.05)。ATG 5的表达水平与肿瘤大小之间的相关性也是显著的(P = 0.02)。CHAST的表达与PR状态显著相关(P = 0.04),并倾向于与ER状态相关(P = 0.05)。最后,NKILA的表达与首次妊娠年龄显著相关(P = 0.01)。在评估基因的表达水平和临床参数之间未检测到其他显著相关性。上述基因的表达水平之间存在显著相关性。CHAST和ADINR之间的相关性最显著(肿瘤组织和ANCT的相关系数分别为0.78和0.69)。基于曲线下面积(AUC)值,DICERI-AS和CEBPA在区分肿瘤组织与ANCT方面具有最佳性能(AUC值分别为0.92和0.90)。联合检测6个基因的转录本量可区分这两组样本,敏感性为92.3%,特异性为91%,诊断能力为95%。本项目重点研究了乳腺癌组织中NF-κ B相关基因的异常表达,提示其可能作为乳腺癌的潜在诊断标志物。
The nuclear factor-kappa B (NF-kappa B) 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-kappa B 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-kappa B 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, DICERI-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-kappa B-associated genes in breast cancer tissues and suggests them as potential diagnostic markers in breast cancer.