The Role And Clinicopathological Significance Of PTEN And Its Related Pathway Genes In Ovarian Serous Carcinoma

Objective:To investigate the role and clinicopathological significance of PTEN and its related pathway genes in ovarian serous carcinoma.Methods:(1)To explore the expression of PTEN and its related pathway genes in ovarian serous carcinoma from the histological aspect.From January2016 to January 2018,40 patients with ovarian serous cancer were collected as experimental group,and 20 non-tumor ovarian tissues(ovarian germinal epithelial inclusion cyst),20 benign serous tumors and 20 borderline serous tumors were collected as control group.Immunohistochemistry was used to detect the expression of PTEN and its related pathway downstream genes in ovarian serous carcinoma and non-tumor ovarian tissues,benign serous tumors and borderline serous tumors.To analyze the expression of PTEN and its related pathway downstream genes in ovarian serous carcinoma and its correlation with clinicopathological features and prognosis.All statistical analyses were carried out by SPSS 22.0(SPSS Inc,Chicago,USA).P value less than 0.05 was statistically significant.(2)To study the mechanism of PTEN-related signaling pathway inducing apoptosis of human ovarian serous cancer cells in cytology.1.Human ovarian serous carcinoma SKOV3 cells were cultured,and PTEN was overexpressed by plasmid transfection,which was verified by Real-time PCR and Western-Blot.2.To observe the effect of PTEN gene overexpression on the proliferation of human ovarian serous cancer cells by CCK8 experiment.3.To observe the effect of PTEN on the migration ability of ovarian serous cancer cells by cell scratch test.4.The effect of PTEN on apoptosis and cell cycle of ovarian serous cancer cells was detected by flow cytometry.5.The effect of PTEN upregulation on the downstream genes p-ERK1and Cyclin D1 in its related pathway was studied by Western-Blot technique.Results:(1)The expression of PTEN and its related pathway downstream genes in ovarian serous tumors:1.Immunohistochemical staining showed that the positive rate of PTEN in ovarian serous tumors was 35%(14/40),which was lower than that in non-tumor ovarian tissues(17/20,85%),benign serous tumors(16/20,80%)and borderline serous tumors(14/20,70%),The expression of PTEN decreased with the occurrence and progression of ovarian serous carcinoma,and the difference was statistically significant(X~2=19.924,P<0.05).However,the positive rate of phosphorylated ERK1 downstream of related pathway in ovarian serous carcinoma tissues was 80%(32/40),which was higher than that in non-tumor ovarian tissues(4/20,20%),benign serous tumor(10/20,50%)and borderline serous tumor tissues(12/20,60%),The expression of p-ERK1 increased with the occurrence and progression of ovarian serous carcinoma,and the difference was statistically significant(X~2=22.385,P<0.05).The positive rate of Cyclin D1 in ovarian serous carcinoma was70%(28/40),which was higher than that in non-tumor ovarian tissue(3/20,15%),benign serous tumor(6/20,30%)and borderline serous tumor(8/20,40%),The expression of Cyclin D1 increased with the occurrence and progression of ovarian serous carcinoma,and the difference was statistically significant(X~2=19.394,P<0.05).2.The expression of PTEN and its related pathway downstream genes p-ERK1 and Cyclin D1 is related to tumor grade,stage and lymph node metastasis of ovarian serous carcinoma(all P<0.05).3.The expressions of PTEN,p-ERK1 and Cyclin D1 were significantly correlated in ovarian serous cancer.PTEN was negatively correlated with p-ERK1(r=-0.419,P<0.05)and Cyclin D1(r=-0.435,P<0.05),while p-ERK1 was positively correlated with Cyclind1(r=0.627,P<0.05).4.Age,grade,stage,lymph node metastasis,PTEN,p-ERK1 and Cyclin D1 are independent factors affecting the survival of serous ovarian cancer after operation.(2)The mechanism of PTEN overexpression inducing apoptosis of human ovarian serous cancer cells:1.Compared with blank control group and negative control group,PTEN overexpression group significantly inhibited the proliferation of ovarian serous cancer cells(P<0.05);And the healing ability of cell scratches was obviously weakened(P<0.05).Compared with blank control group(t=14.7,P<0.05)and negative control group(t=14.2,P<0.05),the apoptosis rate of ovarian serous cancer cells treated by PTEN overexpression was significantly higher.The proportion of cells in S phase of cell cycle increased significantly.2.After overexpression of PTEN plasmid transfected cells,compared with blank control group and negative control group,the expression of p-ERK1 and Cyclin D1 proten in SKOV3 cells with PTEN overexpression were obviously inhibited,and the difference was statistically significant(all P<0.05).Conclusion:1.The expression of PTEN in ovarian serous carcinoma is generally lower than that in non-tumor ovarian tissues,benign serous tumors and borderline serous tumors.The expression levels of p-ERK1 and Cyclin D1 in ovarian serous carcinoma were higher than those in non-tumor ovarian tissues,benign serous tumors and borderline serous tumors.The expression of PTEN is negatively correlated with the expression of p-ERK1 and Cyclin D1,respectively.The negative expression of PTEN and the positive expression of p-ERK1 and Cyclin D1 are related to the poor clinicopathological features of ovarian serous carcinoma,which indicates that PTEN is a tumor suppressor gene,which may promotes the expression of oncogenes p-ERK1 and Cyclin D1after mutation,and then participates in the occurrence,proliferation,migration and metastasis of ovarian serous carcinoma.2.PTEN overexpression may inhibit the proliferation and migration of ovarian serous cancer cells SKOV3,promote the apoptosis of ovarian serous cancer cells and inhibit the cancer cell cycle in S phase by inhibiting the expression of downstream genes p-ERK1/2 and Cyclin D1 in ovarian serous cancer cells.