Based on the NF-κB signaling pathway to explore the predictive effect of DNA repair gene PARP1 on distant metastasis after Breast cancer surgery

Abstract

Abstract Backgroud: To study the expression of the expression of NF-κB proteins (IKKβ, p50, p65, TNF-α) and PARP1 in patients with distant metastasis and non-metastasis after Breast cancer surgery, and analyze their correlation. Their immunohistochemical scores were used to predict their effect on postoperative distant metastases in Breast cancer patients. Methods：Nested case-control study was used. Patients with distant metastasis in the Breast cancer follow-up cohort established in 2014 were selected as the metastasis group, while non-metastasis were selected as the control group. Immunohistochemical methods were used to detect the expression of NF-κB proteins (IKKβ, p50, p65, TNF-α) and PARP1 in the Breast cancer patients. ROC was used to analyze the predictive effect of these on distant metastasis after Breast cancer surgery. COX model was used to evaluate the effects of PARP1 and TNF-α on distant metastasis after Breast cancer surgery. Results: (1) PARP1 was mainly expressed in the nucleus of Breast cancer cells. IKKβ, p50, p65 and TNF-α proteins were mainly expressed in the cytoplasm. And the Immunohistochemical score of them both are significantly higher in the group of distant metastasis than non-metastasis (P<0.001).(2) PARP1 was correlated with IKKβ, p50, p65 and TNF-α proteins (P<0.001). There was a correlation between IKKβ, p50, p65 and TNF-α proteins (P<0.001). (3) ROC curve showed that PARP1>6, IKKβ>4, p65>4, p50>2, TNF-α>4 had a predictive effect on distant metastasis.(SePARP1=78.4%, SpPARP1=79.4%, AUCPARP1=0.843; SeIKKβ=51.55%, SpIKKβ=64.95%, AUCIKKβ=0.591; Sep65=88.66%, Spp65=46.39%, AUCp65=0.716; Sep50=60.82%, Spp50=69.07%, AUCp50=0.6884; SeTNF-α=64.95%, SpTNF-α=70.10%, AUCTNF-α=0.709.)(4) COX analysis showed that the high expression of PARP1 and TNF-α were risk factors for distant metastasis after Breast cancer surgery (RRPARP1=4.092, 95%CI:2.475-6.080, P<0.001),(RRTNF-α=1.825, 95%CI:1.189-2.779, P=0.006). Conclusion:(1)PARP1, IKKβ, p50, p65 and TNF-α were positively correlated with distant postoperative metastasis of Breast cancer.(2) When PARP1>6, IKKβ>4, p50>2, p65>4, TNF-α>4, it has a certain predictive effect on postoperative metastasis of Breast cancer;(3)PARP1 may regulate the effect of TNF-α on Breast cancer metastasis through NF-κB signaling pathway, providing clues for the molecular mechanism of Breast cancer metastasis.