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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.
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Objective: To analyze the expression of hypoxia-inducible factor-1α (HIF-1α) and survivin in breast cancer, and different molecular subtypes of breast cancer and to assess their relationship with recurrence and prognosis. Methods: The expression levels of HIF-1α and survivin genes in breast cancer were investigated using bioinformatics. Their protein expression levels were then verified through immunohistochemistry (IHC), and their relationship with recurrence and prognosis was assessed. Results: Expression levels of HIF-1α and survivin genes and proteins were increased in breast cancer tissues compared with normal tissues. Both were associated with clinical features of breast cancer and differentially expressed in different molecular subtypes of breast cancer, and both are related to the signal pathway of breast cancer growth and invasion. HIF-1α and survivin gene and protein expression levels were correlated, and both were associated with breast cancer recurrence (R = 0.380, P < 0.05; R = 0.673, P < 0.05, respectively). According to The Cancer Genome Atlas (TCGA) database, HIF1A and BIRC5 gene were not associated with breast cancer prognosis (P ≥ 0.05); however, HIF-1α and survivin protein were associated with recurrence patient's overall survival (OS) (P < 0.05). Conclusion: HIF-1α and survivin are highly expressed in breast cancer and can be used as potential biomarkers to predict recurrence and assess prognosis.
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BACKGROUND: This study explores the effect of different registration methods on the placement accuracy and dosimetric analysis of adaptive radiation therapy (ART) after breast conserving surgery for breast cancer, based on cone-beam computed tomography (CBCT). METHODS: Thirty breast cancer patients, who underwent breast conserving surgery, were divided into three groups, with 10 patients in each group: automatic grayscale registration (group A), automatic bony marker registration (group B), and automatic grayscale registration combined with manual bony marker registration (group C). Three registration methods were conducted before the first radiotherapy, and once a week under the guidance of CBCT. The dosimetric comparison was made with the original plan. RESULTS: The X direction was significantly different between groups A and B (P=0.036). The X and Y direction were significantly different between groups A and C (P=0.001, P=0.019). The placement errors were significantly different between groups B and C in the X and Y directions (P<0.001, P=0.003). The ART plan was significantly better than the original plan, in terms of the Dmax, Dmean, D90, V90, V100, V95, HI and CI of planning target volume (PTV) (P<0.05). Furthermore, the ART plan was significantly better, in terms of the Dmean, V5, V10, V20 and V30 of the affected lung, the Dmean, V5, V10, V20 and V30 of the double lung, and the Dmean, V5, V10, V20 and V30 of the heart. Moreover, the Dmax, V5 and V10 of the contralateral breast were significantly lower than those in the original CT plan (P<0.05). CONCLUSIONS: For the CBCT placement verification after breast conserving surgery, the accuracy and stability of automatic gray-scale registration combined with manual bone markers are better than those of the automatic gray-scale registration and automatic bone marker registration.