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核因子-κB(NF-κB)和生存素在乳腺癌中的意义及其与放射敏感性和预后的关系

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

作者信息

Cao Qian, Ai Xiu-Qing, Mushajiang Munire

机构信息

Department of Breast Radiotherapy, The Third Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Urumqi, Xinjiang, 830011, People's Republic of China.

出版信息

Breast Cancer (Dove Med Press). 2023 Mar 9;15:175-188. doi: 10.2147/BCTT.S399994. eCollection 2023.

DOI:10.2147/BCTT.S399994
PMID:36923396
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10010128/
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 (<0.05). In different molecular subtypes of breast cancer, NFKB1 and BIRC5 were differentially expressed (<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 (<0.05), and BIRC5 expression is higher in BL-2 than other subtypes (<0.05). NFKB1 was not associated with tumour size, lymph node stage and distant metastasis (≥0.05), while BRIC5 was associated with these clinical features (<0.05). NF-κB and survivin genes were negatively correlated (R = - 0.193, <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 (≥0.05). The mRNA levels of the both were not correlated with breast cancer subtypes (≥0.05). The mRNA expression of NF-κB and survivin correlated with distant metastasis. NF-κB and survivin mRNAs were positively correlated (=0.903, <0.05). Gene and mRNA expression of NF-κB and survivin were not associated with patients' survival overall survival (OS) (≥0.05). Down-regulation of survivin has little effect on the proliferation rate of breast cancer cells (≥0.05), but increase the apoptosis rate of breast cancer cells (<0.05).The proliferation rate of cells decreased and the apoptosis rate increased significantly (<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.

摘要

目的

分析核因子κB(NF-κB)和生存素(survivin)基因及mRNA在乳腺癌中的表达情况,评估其对预后的影响,并研究它们与乳腺癌放射敏感性的关系。

方法

采用生物信息学方法分析乳腺癌中NF-κB和survivin基因的表达水平,通过逆转录聚合酶链反应(RT-PCR)验证NF-κB和survivin mRNA,并评估它们与预后的关系。使用小干扰RNA(siRNA)敲低survivin,分析其与乳腺癌放射敏感性的关系。

结果

NFKB1和BIRC5的基因表达在多种肿瘤及其相应的正常组织类型中存在差异。在乳腺癌组织中,与正常组织相比,NFKB1表达水平降低,而BIRC5表达水平升高(<0.05)。在乳腺癌的不同分子亚型中,NFKB1和BIRC5表达存在差异(<0.05),NFKB1在管腔亚型中高表达,BIRC5在三阴性乳腺癌(TNBC)亚型中高表达。在TNBC亚型中,免疫调节(IM)亚型的NFKB1表达高于其他亚型(<0.05),基底样2(BL-2)亚型的BIRC5表达高于其他亚型(<0.05)。NFKB1与肿瘤大小、淋巴结分期和远处转移无关(≥0.05),而BIRC5与这些临床特征相关(<0.05)。NF-κB和survivin基因呈负相关(R = -0.193,<0.05)。在乳腺癌患者中,NF-κB和survivin的mRNA水平呈相同趋势表达。复发和未复发患者中NF-κB和survivin无显著差异(≥0.05)。二者的mRNA水平与乳腺癌亚型无关(≥0.05)。NF-κB和survivin的mRNA表达与远处转移相关。NF-κB和survivin的mRNA呈正相关(=0.903,<0.05)。NF-κB和survivin的基因及mRNA表达与患者的总生存期(OS)无关(≥0.05)。survivin的下调对乳腺癌细胞的增殖率影响不大(≥0.05),但可增加乳腺癌细胞的凋亡率(<0.05)。放疗后细胞增殖率降低,凋亡率显著增加(<0.05),该技术可提高乳腺癌细胞的放射敏感性。

结论

NF-κB和survivin在基因和mRNA水平相互作用。调节NF-κB或survivin的mRNA表达可能有助于提高乳腺癌细胞的放射敏感性,未来还需要更多实验加以验证。

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