Preliminary Studies On The Function And Mechanism Of Peroxidase(PXDN) In Ovarian Cancer

1.BackgroundOvarian cancer is one of the common tumors in women,and it is also the highest mortality gynecological tumor.The pathogenesis is still unclear.Abnormal activation of oncogenes or inactivation of tumor suppressor genes play a key role in the development of tumors.Peroxidase(PXDN)is closely related to many diseases such as renal fibrosis and tumorigenesis.The function and related mechanisms of PXDN in ovarian cancer,especially serous ovarian cancer,are unclear.This study aimed to investigate the functional and potential mechanisms of PXDN in ovarian cancer.2.Objection(1)Defining the clinical significance of PXDN in ovarian cancer(2)To determine whether PXDN affects the proliferation and invasion of ovarian cancer cells(3)Preliminary study on how PXDN promotes proliferation,invasion and metastasis of ovarian cancer cells3.Methods(1)We compared the expression of PXDN in normal ovarian and ovarian cancer tissues through TCGA and Kaplan-Meier Plotter databases,and evaluated the potential clinical significance of PXDN.And we verified the expression of PXDN in serous ovarian cancer tissues by immunohistochemistry.(2)We verified the expression of PXDN in ovarian cancer cell lines by RT-PCR and Western blotting.We interfered with the expression of PXDN in ovarian cancer cell lines SKOV3 and OV15 by siRNA,and further we used CCK8 proliferation assay and colony formation assay to detect the effect of PXDN on proliferation and drug resistance of ovarian cancer cells;then we passed the transwell and scratch assay.The effect of PXDN on the invasion and metastasis of ovarian cancer cells SKOV3 and OV15 was examined.(3)We used RT-PCR and Western blotting to detect key molecular mechanisms that promote the proliferation and invasion of ovarian cancer cells.4.Results1.By analyzing the expression of PXDN in 212012-at chip in TCGA and GTEx database,PXDN expression was significantly increased in 586 serous ovarian cancer samples compared with 8 normal ovarian tissue samples.The relationship between PXDN expression in 212012-at and progression-free survival and overall survival was analyzed by kaplan-meier plotter database.It was found that 715 patients with high expression group had no progression survival compared with 720 patients with low expression.The period was significantly shortened(p<0.001);compared with 828 cases of low expression,the overall survival of patients in the 828 high expression group was significantly shorter(p<0.001).2.Immunohistochemical results suggest that 11 cases of high expression of PXDN in benign ovarian cysts,126 cases of low expression,serous ovarian cancer group:PXDN high expression of 55 cases,low expression of 24 cases,statistical analysis found that benign ovarian cysts and Serous ovarian cancer was statistically significant(p<0.001).We also analyzed the relationship between pathological grade and PXDN expression,and classified the pathological grade into high grade(low expression of 7 cases,high expression of 33 cases)and low grade(low expression of 17 cases,high expression of 22 cases),using chi-square X2 Statistical analysis showed that PDXN was positively correlated with pathological grade of ovarian cancer p:0.012.3.Using the expression of interfering PXDN,the results showed that the proliferation,invasion and metastasis ability of ovarian cancer SKOV3 and OV15 cells in the interference group were significantly inhibited The effect of low expression of PXDN on the resistance of ovarian cancer cells to cisplatin or paclitaxel was not found in this study..4.This study found that the molecular mechanism of PXDN promoting proliferation,invasion and metastasis of ovarian cancer is related to the promotion of Snail1 and Smad4 expression and activation of Smad2 and Smad3 in the TGF-?pathway.5.Summary1.PXDN is significantly elevated in serous ovarian cancer tissues and has potential value as a prognostic marker.2.Expression of PXDN can inhibit the proliferation,invasion and metastasis of ovarian cancer cells.3.The molecular mechanism of PXDN inhibiting the invasion and metastasis of ovarian cancer is related to the repression of the expression of snail1 and Smad4 and the inactivation of Smad2 and Smad3.