Significance of Nuclear Factor-Kappa B (NF-κB) and Survivin in Breast Cancer and Their Association with Radiosensitivity and Prognosis.

Abstract

Purpose: Analyze the expression of NF-κB and survivin genes and mRNAs in breast cancer, and evaluate their impact on prognosis. Investigate their association with radiosensitivity in breast cancer.

Methods: The expression levels of NF-κB and survivin genes in breast cancer were analyzed by bioinformatics, NF-κB and survivin mRNA was verified by RTRCR, and their association with prognosis were assessed. Knockdown of survivin by siRNA was used to analyze its association with radiosensitivity in breast cancer.

Results: The gene expression of NFKB1 and BIRC5 are differentially expressed in a variety of tumours and their corresponding normal tissue species. In breast cancer tissues, NFKB1 expression levels were reduced compared to normal tissue, while BIRC5 expression levels were increased (P<0.05). In different molecular subtypes of breast cancer, NFKB1 and BIRC5 were differentially expressed (P<0.05), NFKB1 was highly expressed in the luminal subtype and BIRC5 was highly expressed in the TNBC subtype. In TNBC subtype, NFKB1 expression is higher in IM subtype than other subtypes (P<0.05), and BIRC5 expression is higher in BL-2 than other subtypes (P<0.05). NFKB1 was not associated with tumour size, lymph node stage and distant metastasis (P≥0.05), while BRIC5 was associated with these clinical features (P<0.05). NF-κB and survivin genes were negatively correlated (R = - 0.193, P<0.05). The mRNA levels of NF-κB and survivin are expressed in the same trend in breast cancer patients. NF-κB and survivin were not significantly different in recurrent and non-recurrent patients (P≥0.05). The mRNA levels of the both were not correlated with breast cancer subtypes (P≥0.05). The mRNA expression of NF-κB and survivin correlated with distant metastasis. NF-κB and survivin mRNAs were positively correlated (R=0.903, P<0.05). Gene and mRNA expression of NF-κB and survivin were not associated with patients' survival overall survival (OS) (P≥0.05). Down-regulation of survivin has little effect on the proliferation rate of breast cancer cells (P≥0.05), but increase the apoptosis rate of breast cancer cells (P<0.05).The proliferation rate of cells decreased and the apoptosis rate increased significantly (P<0.05) after the implementation of radiotherapy, and this technique could improve the radiosensitivity of breast cancer cells.

Conclusion: NF-κB and survivin interact at the gene and mRNA levels. Regulation of mRNA expression of NF-κB or survivin may help to improve the radiosensitivity of breast cancer cells, more experiments are needed to verify this in the future.