Correlation Analysis Of Calcyclin Binding Protein With The Efficacy Of Neoadjuvant Chemotherapy And Prognosis Of Breast Cancer

Objective:This study aimed to explore the expression of calcyclin binding protein/Siah-1interacting protein(Cacy BP/SIP)in breast cancer and to retrospectively analyze the clinical case data of the patients,as well as the correlation between Cacy BP/SIP and the efficacy of neoadjuvant chemotherapy and long-term prognosis of breast cancer patients.This study was expected to provide valuable clinical data for selecting individual treatment strategies and improving the effective rate of neoadjuvant chemotherapy for breast cancer.Methods:A retrospective study of 110 breast cancer patients admitted to the Breast Disease Diagnosis and Treatment Center of the Affiliated Hospital of Qingdao University from January 2016 to December 2017 was conducted.All breast cancer patients underwent neoadjuvant chemotherapy and the clinical and follow-up data of them were collected.En Vision immunohistochemical staining method was used to detect the expression of Cacy BP/SIP in tumor specimens before chemotherapy.The high or low expression of Cacy BP/SIP was defined according to the comprehensive score of Cacy BP/SIP staining intensity and positive cell proportion.Chi-squared test and Spearman correlation analysis were used to compare the classification data between groups to explore the clinicopathological indicators related to Cacy BP/SIP expression.Treatment response of neoadjuvant chemotherapy was evaluated by the clinical and pathological efficacy evaluation system.Chi-squared test and Fisher’s exact probability method were performed to screen the factors related to efficacy.Correlation between Cacy BP/SIP and treatment response was analyzed by binary Logistic regression model.Cumulative disease-free survival rate of the breast cancer patients was presented by Kaplan-Meier method and we compared differences between groups by Log-rank test.Finally,Cox proportional risk regression model was made for predicting the independent factors of disease-free survival(DFS)of all patients.Results:1.A total of 110 breast cancer patients were enrolled in this study.71 cases(64.5%)showed high expression of Cacy BP/SIP(score>5)and 39 cases(35.5%)showed low expression(score≤5).Chi-squared test showed that the high expression of Cacy BP/SIP was significantly correlated with higher histological grade(χ~2=7.314,P=0.026),advanced clinical lymph node stage(χ~2=8.870,P=0.012),and advanced clinical TNM stage(χ~2=7.099,P=0.008).Spearman correlation analysis further verified the correlation between factors above:Cacy BP/SIP was positively correlated with histological grade(r=0.239,P<0.05),clinical lymph node stage(r=0.277,P<0.01)and clinical TNM stage(r=0.257,P<0.01).There was no significant correlation between Cacy BP/SIP and other indexes(age,menstrual status,hormone receptor expression,molecular typing,etc.)(P>0.05).2.Clinical objective response was achieved in 85 breast cancer patients after neoadjuvant chemotherapy,and the objective response rate was 77.3%(85/110).The disease control rate was 94.5%(104/110)and pathologic complete remission(p CR)rate was 14.5%(16/110).Univariate analysis was used to preliminarily screen the relevant variables of clinical objective response,which included Cacy BP/SIP,maximum diameter of primary tumor,clinical lymph node stage,human epidermalgrowth factor receptor-2(HER-2)expression and molecular typing.Binary Logistic multivariate regression analysis suggested Cacy BP/SIP(P=0.039,OR=0.201,95%CI:0.048-0.845),maximum diameter of primary tumor(P=0.007,OR=0.152,95%CI:0.039-0.595)and HER-2 expression(P=0.006,OR=4.697,95%CI:1.561-14.132)were independent influencing factors of objective response in neoadjuvant chemotherapy.Univariate analysis showed that the relevant variables of p CR included Cacy BP/SIP,clinical lymph node stage and estrogen receptor(ER)expression.Binary Logistic multivariate regression analysis indicated that only Cacy BP/SIP(P=0.038,OR=0.268,95%CI:0.077-0.852)and ER expression(P=0.034,OR=0.218,95%CI:0.051-0.857)were independent factors of p CR.3.In terms of survival prognosis,the overall disease-free survival rate of follow-up patients was 89.1%(98/110).Kaplan-Meier survival curve was plotted and statistical analysis revealed that the disease-free survival of Cacy BP/SIP low-expression group was significantly better than that of high-expression group(92.3%vs.87.3%,χ~2=4.824,Log rank P=0.028).Multivariate analysis of COX regression model failed to confirm that Cacy BP/SIP(P=0.154,HR=0.339,95%CI:0.074～1.546)was an independent influencing factor of DFS,only p CR was significantly correlated with it(P=0.043,HR=0.216,95%CI:0.014-0.758).Conclusion:Abnormal up-regulation of Cacy BP/SIP was closely associated with the malignant progression of breast cancer.High expression of Cacy BP/SIP has been proven to be an independent risk factor for clinical and pathological outcomes after neoadjuvant chemotherapy.In our study,patients with low Cacy BP/SIP expression had better disease-free survival than those with high Cacy BP/SIP expression.However,its independent predictive value for survival outcome needs to be further studied.