Based On The NF-κB Signaling Pathway To Explore The Effect Of DNA Repair Gene PARP1 On Distant Metastasis After Breast Cancer Surgery

Objective:To investigate the expression of PARP1,IKKβ,P50,P65and TNF-αin postoperative patients with breast cancer,and analyze the their correlations;the expression of IKKβ,p50,p65 and TNF-αproteins in NF-κB signaling pathway and PARP1was further discussed to predict and influence the postoperative metastasis of breast cancer.Methods:A total of 194 patients were selected from the breast surgery Department of the Affiliated Hospital of Southwest Medical University to establish a nested pathological control study.According to1:1 matching design,immunohistochemical methods were used to detect the expression of IKKβ,p50,p65 and TNF-αproteins in NF-κB signaling pathway and PARP1 in paraffin specimens of the two groups of breast cancer patients.ROC was used to analyze the predictive effect of these on distant metastasis after breast cancer surgery.Logistic regression model was used to evaluate the effects of PARP1 and TNF-αon distant metastasis after breast cancer surgery.Results:（1）PARP1 was mainly expressed in the nucleus of breast cancer cells,and a small part was expressed in the cytoplasm.The IHC score of PARP1 was significantly higher in the group with distant metastasis after breast cancer surgery than in the group without metastasis（Z=8.4,P<0.001）.（2）IKKβ,p50,p65 and TNF-αproteins in NF-κB signaling pathway were mainly expressed in the cytoplasm,and the IHC score in the group with distant metastasis after breast cancer surgery was significantly higher than that in the group without metastasis（P<0.001）.（3）Spearman rank correlation analysis showed that IKKβ,p50,p65 and TNF-αproteins in NF-κB signaling pathway and PARP1 were positively correlated（P<0.001）.All were associated with distant postoperative metastasis of breast cancer（P<0.001）.（4）ROC curve analysis showed that PARP1>6,IKKβ>4,p65>4,p50>2,TNF-α>4 had a certain predictive effect on distant metastasis after breast cancer surgery(Se_PARP1=78.4%,Sp_PARP1=79.4%,AUC_PARP1=0.843;Se_IKKβ=51.55%,Sp_IKKβ=64.95%,AUC_IKKβ=0.591;Se_p65=88.66%,Sp_p65=46.39%,AUC_p65=0.716;Se_p50=60.82%,Sp_p50=69.07%,AUC_p50=0.6884;Se_TNF-α=64.95%,Sp_TNF-α=70.10%,AUC_TNF-α=0.709).（5）Logistic regression analysis showed that high and low expression of PARP1 and TNF-αwere risk factors for distant metastasis after breast cancer surgery(OR_PARP1=4.574,95%CI:2.746～7.618,P<0.001)、(OR_TNF-α=1.911,95%CI:1.242～2.940,P=0.003).Conclusion:（1）PARP1,IKKβ,p50,p65,and TNF-αwere positively correlated,and they were related to postoperative distant metastasis of breast cancer,suggesting that PARP1 might regulate the expression of TNF-αthrough NF-κB signaling pathway to play a role in the distant metastasis of breast cancer.（2）When the immunohistochemical score PARP1>6,IKKβ>4,p50>2,p65>4,TNF-α>4,it has a certain predictive effect on postoperative metastasis of breast cancer.