Expression Of CYP4501B1 And COMT Protein In Human Endometrial Cancer

Objective: In recent years, the incidence of endometrial cancer is on the rise, becoming the third gynecologic cancer of threating women's health after breast and ovarian cancer. At present, the pathogenesis of endometrial cancer is not clear. It is considered as risk factors that long-term estrogen exposure without progesterone against, and physical factors. However, with the research to the estrogen, it is gradually discovered that estrogen metabolites have a closer relationship with tumor occurrence and development. And it is reported in a large number of literature that estrogen metabolites -catechol estrogen and quinone can directly cause DNA damage and mutation, then induce cancer occurrence. Cytochrome P4501B1(CYP1B1) is involved in estrogen metabolism , whose metabolites are associated with the initiation and progression of cancer. catechol-O-methyltransferase (COMT) converts those metabolites to nontoxic substances and cleans them out of body. Therefore both enzymes play an important role in endometrial carcinogenesis and development. The study was to detect the CYP1B1, and COMT protein expression in endometrial cancer and normal endometrial tissues, then to provide a theoretical basis for the clinical diagnosis, treatment and pathogenesis of endometrial cancer.Methods:Western blot was used to detect the expression of CYP1B1, COMT protein in 39 endometrial cancer and 22 normal endometrial tissues, then to compare the differences.Statistical analysis was performed using SPSS13.0 software package. P<0.05 was considered significant for all statistical analysis. The normality of protein expression level was analyzed by the test of normality. Comparison of two groups was performed by the t-test and three groups by the One-Way ANOVA , if the groups have a significant difference, Comparison of two groups by SNK, P<0.05 was considered significant for all statistical analysis. If have uneven variance, Comparison of two groups was performed by the non-parametric test.Results:1. The distributions of the CYP1B1 and COMT protein expression were normal.2. The relative expression of CYP1B1 in the case group was significantly higher, the difference was statistically significant (P = 0.003); while the S-COMT, M-COMT expression in the case group was significantly lower than the control group, the difference was statistical significance (P = 0.001, P = 0.000).3. Since COMT catalyzes the products of CYP1B1, the ratios between the expression of CYP1B1 and COMT were calculated. The CYP1B1/S-COMT and CYP1B1/M-COMT in the endometrial cancer patients were significantly higher than controls , the difference was statistically significant(P =0.000, P =0.000).4. Case group was divided into stageⅠ,ⅡandⅢ, the expression of CYP1B1 in the three phase is significant difference (P = 0.000), and according toα= 0.05 level the results of SNK multiple comparison test show that between every two groups the expression of protein were significantly different, that is, stageⅢendometrial cancer have the highest expression levels of CYP1B1, stageⅠendometrial cancer have the lowest levels; the expression of M-COMT were not significantly different between the three stages (P = 0.550 ), the expression of S-COMT in the three stage were significantly difference (P=0.001), but CYP1B1/S-COMT and CYP1B1/M-COMT in the three period werw statistically differences (P = 0.000, P = 0.003 ).Conclusion:1. CYP1B1 in endometrial cancer tissues is highly expressed, while in the normal tissues, its levels are lower, indicating that CYP1B1 may play an important role in the occurrence of endometrial cancer ;2. CYP1B1 in advanced endometrial carcinoma was significantly higher than early stage, suggesting that CYP1B1 may be the prognostic indicators for endometrial cancer;3. The increase of CYP1B1/COMT shows that in endometrial cancer, the levels of the two enzymes are out of balance, too much estrogen and estrogen metabolites can not be out of the body, resulting in the occurrence of endometrial cancer;4.Lower expression of COMT in endometrial cancer tissues may play an important roel in the occurrence of endometrial cancer;and the level of S-COMT is related to the different clinical stage.