| Background and Objective:The responsiveness of breast cancer to chemotherapy is highly individualized.Using in vitro drug sensitivity technology to predict the sensitivity of individual tumors to chemotherapy drugs to treat breast cancer can achieve the purpose of precise treatment.This paper aims to test the accuracy of HDST drug sensitivity technology,explore the relationship between the inhibition rate and sensitivity rate of different chemotherapeutic drugs on breast cancer tissue,the relationship between chemotherapeutic drugs and drug resistance proteins,and the relationship between drug resistance proteins and breast cancer molecular markers The relationship between the two,so as to guide the clinical medication.Method:A total of 59 patients who were diagnosed as invasive breast cancer by preoperative biopsy at the first diagnosis in Nanchang Third Hospital from June 2020 to June 2021 were enrolled.The inhibition rate and sensitivity rate of 8 single drugs of carboplatin,gemcitabine,capecitabine,docetaxel,paclitaxel,cyclophosphamide,doxorubicin,epirubicin and doxorubicin combined with cyclophosphamide and epirubicin combined with cyclophosphamide were determined by HDST in vitro tissue drug sensitivity technique in 59 cases of breast cancer.The patient survival data were collected and the accuracy of HDST was analyzed.Immunohistochemical method was used to detect the expression of P-GP,BCRP,Top2 a,TUBB3 and Tau proteins in breast cancer tissues,and further analyze the relationship between chemotherapeutic drug sensitivity and drug resistance proteins,so as to verify the accuracy of HDST technology for drug screening.The ability of HDST technique and drug-resistant protein in predicting tumor recurrence and metastasis was compared.Result:1.The inhibition rates of different chemotherapy drugs on breast cancer tissues were significantly different.The inhibition rates of single drug group from high to low were paclitaxel,doxorubicin,epirubicin,docetaxel,capecitabine,gemcitabine,carboplatin and cyclophosphamide.The inhibition rate of doxorubicin and cyclophosphamide in the combination group was higher than that of epirubicin and cyclophosphamide.The sensitivity rates of different chemotherapy drugs to breast cancer tissues were from high to low,which were taxol,docetaxel,doxorubicin,carboplatin,epirubicin,capecitabine,gemcitabine and cyclophosphamide.The sensitivity rate of doxorubicin and cyclophosphamide in the combination group was higher than that of epirubicin and cyclophosphamide.There were significant differences in the inhibition rate among different chemotherapy drugs(F=16.586 P< 0.05).There were significant differences in sensitivity rates among different chemotherapy drugs(X2=71.396 P < 0.05).There was no significant difference between paclitaxel and doxorubicin in the inhibition rate of breast tumor tissue,but there was significant difference between paclitaxel and doxorubicin compared with other drugs(P < 0.05).There was no significant difference in the inhibition rate between cyclophosphamide and gemcitabine and carboplatin on breast tumor tissue,but there was a significant difference between cyclophosphamide and other chemotherapy drugs(P<0.05).2.In breast cancer tumor tissues,the drug resistance of doxorubicin in p-GP positive group was significantly higher than that in P-GP negative group,with statistical significance(P<0.05);Paclitaxel resistance in p-GP positive group was significantly higher than that in P-GP negative group,the difference was statistically significant(P <0.05).The drug resistance of doxorubicin in BCRP positive group was significantly higher than that in BCRP negative group,the difference was statistically significant(P <0.05).Paclitaxel resistance in BCRP positive group was significantly higher than that in BCRP negative group,the difference was statistically significant(P< 0.05).The sensitivity of doxorubicin in TOP2 a protein positive group was significantly higher than that in TOP2 a protein negative group,the difference was statistically significant(P< 0.05).The paclitaxel resistance in TUBB3 positive group was significantly higher than that in TUBB3 negative group,and the difference was statistically significant(P< 0.05).Paclitaxel resistance in Tau white positive group was significantly higher than Tau negative group,the difference was statistically significant(P<0.05).There was no significant correlation.3.Among 59 breast cancer patients,ER positive and HER2 high expressions in BCRP positive group were significantly higher than those in BCRP negative group,with statistical significance(P<0.05);The expression of ER negative and Ki67 in TOP2 a protein positive group was significantly higher than that in TOP2 a protein negative group,the differences were statistically significant(P<0.05).ER positive and PR positive in Tau positive group were significantly higher than Tau negative group,with statistical significance(P<0.05).There was no significant correlation.4.The total agreement rate between drug sensitivity test results and clinical treatment results was 93.2%,the sensitivity of prediction was 85.7%,the specificity was 94.23%,the positive predictive value was 66.6%,and the negative predictive value was 98%.The prediction results of HDST were in good agreement with the actual clinical chemotherapy efficacy(Kappa=0.711 P <0.05).5.The PREDICTION AUC of HDST for breast cancer recurrence and metastasis by ROC curve analysis was 0.900,indicating high diagnostic accuracy.De Long’s test showed that the diagnostic efficiency of HDST was better than that of P-GP,but the results were not statistically significant(P = 0.082).The diagnostic efficiency of HDST was better than that of BCRP,and the result was statistically significant(P = 0.010).Conclusion:1.HDST is a relatively simple procedure with short time period,the determination results objectively,high stability,feasibility and prediction results and the actual clinical chemotherapy efficacy results are in good consistency of chemotherapy for breast cancer patients chemotherapy prediction scheme provides a new,is a worthy of popularization and application of the chemotherapy drug screening experiment technology.2.The results of HDST in vitro tissue drug sensitivity technique showed that there were differences in inhibition rates among different chemotherapy drugs.3.Relationship between drug-resistant proteins and chemotherapy drugs: high expression of P-GP protein,high expression of BCRP protein and low expression of TOP2 a protein were correlated with drug resistance of Doxorubicin,indicating that these three proteins were involved in drug resistance of Doxorubicin in breast cancer.The high expression of p-GP protein,BCRP protein,TUBB3 protein and Tau protein in breast cancer is correlated with drug resistance to paclitaxel,suggesting that these three proteins are involved in drug resistance to paclitaxel.The accuracy of HDST technology is verified from the side.4.ROC curve analysis showed that the diagnostic efficiency of HDST was better than that of BCRP protein,and the result was statistically significant(P = 0.010).The diagnostic efficiency of HDST was better than that of P-GP protein,but the results were not statistically significant(P = 0.082). |
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