The Expression And Clinical Significance Of PXR,MDR1,CYP3A5 And CYP2B6 In High Grade Serous Ovarian Cancer

Objective: To analyze the expression level of progesterone X receptor(PXR),multidrug resistance protein 1(MDR1),cytochrome P450 3A5(CYP3A5)and cytochrome P450 2B6(CYP2B6)in high grade serous ovarian cancer(HGSOC)tissues and the difference between the chemoresistance group and the sensitive group,and to explore the relationship between them and HGSOC chemotherapy resistance,clinicopathological characteristics,and try to find out the chemosensitivity index of HGSOC patients,so as to provide more theoretical basis for the individualized treatment of HGSOC.Methods: The ovarian tumor tissue samples of 56 HGSOC patients admitted to Qingdao Municipal Hospital from January 2019 to December 2021 were selected as the study subjects.They were divided into drug resistant group(24 cases)and sensitive group(32 cases)according to whether they were sensitive to chemotherapy;At the same time,16 cases of umbrella of normal fallopian tube(UNF)from patients with uterine fibroids were selected as the control group.The expression of PXR,MDR1,CYP3A5 and CYP2B6 in HGSOC and UNF tissue samples was determined by immunohistochemistry(SP two-step method),real-time fluorescence quantitative PCR and western blot(WB).Collect the general information of HGSOC and UNF group,collect the clinicopathological data of HGSOC patients and follow them up.SPSS 20.0 statistical analysis software was used to process the data.t-test was used for comparison of two independent groups.?2 test was used to categorical variables.The correlation between PXR and MDR1,CYP3A5 and CYP2B6 was analyzed by Spearman rank correlation.Results: 1.Comparison of the expression of PXR,MDR1,CYP3A5 and CYP2B6 in HGSOC patients and UNF controls:(1)Immunohistochemical test results: the positive expression rates of PXR,MDR1,CYP3A5 and CYP2B6 in HGSOC patients were 71.4%,75.0%,73.2% and 76.8%,respectively,which were significantly higher than those in UNF controls(12.5%,25.0%,18.8% and 25.0%),with significant differences(P<0.05respectively).(2)PCR results showed that the relative expression of PXR,MDR1,CYP3A5 and CYP2B6 m RNA in HGSOC patients was significantly higher than that in UNF controls(t=12.634,9.264,11.888,6.544,P<0.05 respectively).(3)WB test results:The expression levels of PXR,MDR1,CYP3A5 and CYP2B6 proteins in HGSOC patients were higher than those in UNF control group(t=11.618,7.821,8.726,9.032,P<0.01 respectively).2.Comparison of the expression of PXR,MDR1,CYP3A5 and CYP2B6 in the HGSOC-resistant group and the sensitive group:(1)Immunohistochemical test results: the positive expression rates of PXR,MDR1,CYP3A5 and CYP2B6 in the HGSOC-resistant group were 87.5%,91.7%,87.5% and 95.8%,respectively,which were significantly higher than those in the HGSOC-sensitive group(59.4%,62.5%,62.5% and62.5%),and the difference was statistically significant(P<0.05 respectively).(2)PCR detection results: The relative expression of PXR,MDR1,CYP3A5 and CYP2B6 m RNA in HGSOC-resistant group was significantly higher than that in HGSOC-sensitive group(t=31.622,24.695,26.940,32.135,P<0.05 respectively).(3)WB test results: The expression levels of PXR,MDR1,CYP3A5 and CYP2B6 protein in HGSOC-resistant group were higher than those in HGSOC-sensitive group(t=29.506,31.430,28.642,39.127,P<0.05 respectively).3.In HGSOC,PXR was positively correlated with the expression of CYP3A5 and CYP2B6(rs=0.332,P=0.013;rs=0.308,P=0.021respectively),but not with MDR1(rs=-0.091,P=0.503).4.The positive expression of PXR,MDR1,CYP3A5 and CYP2B6 was associated with lymph node metastasis and postoperative recurrence in HGSOC patients(P<0.05 respectively).The patients with positive expression of PXR,MDR1,CYP3A5 and CYP2B6 had higher rate of lymph node metastasis and postoperative recurrence.Conclusion:(1)The higher expression of PXR,MDR1,CYP3A5 and CYP2B6 may be involved in the occurrence and development of HGSOC,and can be used for the auxiliary diagnosis of HGSOC.(2)PXR,CYP3A5 and CYP2B6 may have synergism in the development of HGSOC.(3)PXR,MDR1,CYP3A5 and CYP2B6 may be related to the high invasion of tumor and can be used to evaluate the prognosis of patients with HGSOC.(4)The expression of PXR,MDR1,CYP3A5 and CYP2B6 can be used to determine the sensitivity of HGSOC to chemotherapy and help provide guidance for postoperative chemotherapy.