Research Progress Of CREPT And CyclinD3 In Epithelial Ovarian Cancer

Research Background and purposeOvarian cancer is one of the most fatal gynecological malignancies in female reproductive system.Ovarian cancer can be divided into four categories according to its location.Epithelial ovarian cancer can be divided into serous carcinoma,mucinous carcinoma,ovarian endometrioid carcinoma,clear cell carcinoma,Brenner tumor and undifferentiated carcinoma according to histological type.In other words,ovarian cancer is a collection of heterogeneous tumors,and epithelial ovarian cancer is the most common type of cancer in this group,accounting for 85 to 90 percent of all ovarian malignancies.Moreover,because of the complex characteristics of the anatomical structure and composition of the female ovary,the early symptoms of most ovarian malignant tumors are not obvious,and once the abdominal distension appears,it is already a metastatic sign,so it is difficult to diagnose.At the time of diagnosis,most of them were late and had poor prognosis.Although pelvic examinations may have the chance to detect ovarian cancer during routine health checkups,they cannot be used as a routine screening method,with more missed diagnoses.Therefore,in order to achieve the goal of secondary prevention of epithelial ovarian cancer,and to safeguard the health and safety of women,it is of great significance to find tumor markers and screening methods for epithelial ovarian cancer at an early stage.It also has important value in monitoring the clinical diagnosis,treatment,prevention,progression,metastasis and prognosis of ovarian cancer.Research methodsA total of 100 cases of paraffin embedded ovarian tissue were randomly selected from gynecology department of affiliated Hospital of Taishan Medical College from July 2010.to July 2017.There were definite pathological diagnosis results after operation,and the relevant data such as clinical records were complete,including 20 cases of normal ovarian tissue,median age of 51 years(46 to 76 years),and 20 cases of benign ovarian tumors,median age was 40 years(26 to 60 years),and 60 cases of epithelial ovarian cancer,with a median age of 52.5 years(37 to 67 years);The 60 cases of malignant ovarian tumors by type of organizationwere divided into three groups,including 35 serous cystadenocarcinoma,15 mucinous and 10 other types of epithelial ovarian cancer.According to FIGO staging criteria,21 cases of stageⅠandⅡand 39 cases of stageⅢandⅣwere divided into two groups.According to histological grade,14 cases were classified as G1 grade,46 cases as G2+G3 grade;According to the results of ascites,39cases were negative in ascites cytology,21 cases were positive in ascites cytology;24cases had lymph node metastasis and 36 cases had no lymph node metastasis according to the routine pathological results of postoperative specimens.All the patients were not treated with chemotherapy and radiotherapy before operation and had no history of other benign and malignant tumors.The subjects of the study were benign ovarian tumors,epithelial ovarian cancer,and normal ovarian tissues(all from patients who were treated with prophylactic hysterectomy plus bilateral appendectomy for benign uterine diseases)as controls.All the collected pathological specimens were fixed by neutral formaldehyde solution,embedded with paraffin at 4-6um thickness,then preserved at 4℃.Immunohistochemical SP method was used to locate the markers in paraffin sections,and the expression of CREPT and CyclinD3 in various ovarian tissues were observed by microscope,And then the professional software system is used to collect maps for statistics and counting.Finally,Several statistical methods,such as Spearman rank correlation analysis,rank sum test and soother statistical methods,were used to deal with and analyze the data systematically and professionally,So all the data were tested by bilateral test.If P<0.05,the difference was statistically significant.Research result1.The positive staining of the positive staining of CREPT and CyclinD3 protein was located in the nucleus and cytoplasm,and all showed brown yellow granules.2.CREPT was positive in normal ovarian tissue,benign ovarian tissue and epithelial ovarian tissue,and the total positive rate was 15%,45%and70%,respectively,and the differential expression of CREPT in three groups of different ovarian tissues was different(χ~2=22.60,P=0.001).There was no significant difference in positive expression between normal tissue and benign ovary(χ~2=4.286,P<0.05).There were significant differences between normal and benign ovarian tissues and epithelial ovarian cancer tissues(χ~2=4.057,P<0.05).Further comparative analysis,the expression of CREPT in epithelial ovarian tissue is not related to the age of the patients,the type of histology,the cytological metastasis of ascites,and the FIGO staging,but related to lymph node metastasis,histological grade.The positive expression of lymph node metastasis in patients with lymph node metastasis was significantly higher than that in patients with negative lymph node metastasis(Z=-2.344,P=0.019),the positive expression in group(G1)was higher than that in group(G2+G3)(Z=-2.030,P=0.042).3.CyclinD3 positive expression was found in normal ovarian tissues,benign ovarian tissues and epithelial ovarian tissues,and the total positive rates were 10%,40%and75%,respectively.The differential expression of CyclinD3 was different in three groups of different ovarian tissues(χ~2=32.40,P=0.000).There was no significant difference in positive expression between normal tissue and benign ovarian tissue(χ~2=4.800,P<0.05),there were significant differences between normal and benign ovarian tissues and epithelial ovarian cancer tissues(χ~2=8.218,P<0.05).Further comparison and analysis of CyclinD3expression in epithelial ovarian tissues,age,histological type,ascitic cytologic metastasis and Figo staging were not relevant,but it is related to histological grade,lymph node metastasis.The positive expression of lymph node metastasis in patients with lymph node metastasis was significantly higher than that in patients with negative lymph node metastasis(Z=-2.320,P=0.020),the positive expression in group(G1)was higher than that in group(G2+G3)(Z=-2.705,P=0.007).4.Spearman rank correlation analysis shows that,the rank correlation coefficient between CREPT and CyclinD3 protein expression in epithelial ovarian neoplasms is r=0.596,the results showed that there was a positive correlation between CREPT and CyclinD3 protein.Conclusion1.The expression of CREPT and CyclinD3 protein in epithelial ovarian carcinoma was higher than that in normal ovarian tissue and benign ovarian tumor tissue.The expression of CREPT and CyclinD3 protein was related to lymph node metastasis and histological grade.These results suggest that CREPT and CyclinD3 proteins may be involved in the development of ovarian cancer.2.There was a positive correlation between the expression of CREPT and CyclinD3in epithelial ovarian cancer tissues,suggesting that the expression of CREPT and CyclinD3might affect each other.3.The combined detection of CREPT and CyclinD3 is expected to be a new index to improve the detection rate of epithelial ovarian cancer and predict the occurrence of ovarian malignancy.