| Even though in the female reproductive system tumor the incidence of Ovarian cancer was lower than that of cervical cancer and endometrial carcinoma, but the mortality is the top of the gynecological tumor. Although primary cytoreductive surgery and Platinum and paclitaxel combination chemotherapy can improve curative effect in patients with ovarian cancer, but the overall 5-year survival rate is still hovering at 30% to 40%. So the research on the origin and development of ovarian cancer, and search for new therapeutic targets effectively, improve the prognosis is still the emphasis and difficulty in ovarian cancer research. In recent years, studies have shown that autophagy is a cellular metabolism is one of the important ways, the inactivation of autophagy regulatory mechanism is closely related to the occurrence of tumor development.Atg5 is one of the important genes involved in the regulation of autophagy, in the extension of autophagy body membrane phase, need two kind of ubiquitin protein system mediated: Atg5- Atg12 combination system is combined with Atg8-PE, Atg5 and Atg12 form compounds, effect on autophagy body membrane surface for the presence of autophagy body membrane, promote the formation of autophagy body, is an important factor of autophagy body form required.Beclinl(BECNI) is a kind of tumor suppressor genes related to the autophagy, a study suggests BECNIallele absent lead to autophagy activity reduced so as to promote the occurrence of tumor. Now is generally accepted that Beclin1 gene encoding protein and Ⅲ PI3K(phosphatidylinositol 3 kinase, phospholipids- 3- hydroxy kinase) form a complex,regulating the Atg1, Atg3 and other Atg protein localization in autophagy precursor structure, which can regulate the activity of autophagy.P53 gene is discovered one of the highest genetic correlation with human tumor so far and have wild type(wild type) and mutant(mutant type), wp53 gene of tumor suppressor genes, mp53 genes for cancer. Mp53 protein half-life is longer(2-12 h), can be detected with immunohistochemical method, and the protein WP53 half-life is very short(20 to 60min), and the content is very low, cannot be detected by immunohistochemical method. The evolution of wild-type P53 by regulating the cell cycle, aging,differentiation to induce cell apoptosis, inhibiting tumor development. Mutant P53 can promote cell proliferation, conducive to the occurrence of tumor development.This study used immunohistochemistry and RT-PCR technique to detect Atg5,Beclin1 and P53 in epithelial ovarian cancer, benign ovarian tumor tissue and expression in normal ovarian tissue and analyze its relationship with ovarian cancer patients with clinical pathological factors and the correlation of three expression, to explore the role of the three in ovarian cancer development, to further understanding of ovarian cancer progress of molecular biology mechanism, which provides the theoretical foundation to guide the clinical treatment and prognosis judgement.ObjectiveDetect autophagy related gene Atg5, Beclin1 and P53 in epithelial ovarian cancer, benign ovarian tumor tissue and the expression of normal ovarian tissue,explore its correlation with ovarian cancer occurrence, development and significance,to study the pathogenesis and treatment of ovarian cancer to provide a new direction.Materials and methods1. The object of study: Collect the third affiliated hospital of zhengzhou university and the first affiliated hospital in September 2013- June 2015 specimensof 84 cases, including sexual ovarian epithelial specimen(malignant group) 34 cases(18 cases of serous carcinoma, 10 cases of mucinous carcinoma, 6 patients with other types). Aged 22 to 78 years old; According to the international department of obstetrics and gynecology clinical staging and pathologic classification standard(FIGO 2000) : phase I in 5 cases; Phase II 9 cases; Phase III 9 cases; Stage IV in 11cases; Pathology classification: G1 9 cases; G2 11 cases; G3 14 cases; 18 cases with lymphatic metastasis, lymphatic metastasis in 16 cases. Benign ovarian tumor tissue(benign group) and normal ovarian tissue(normal group), 25 cases of normal ovarian tissue derived from the line because of uterine myoma and uterine adenomyosis uterine and ovarian tumor, single/double attachment samples confirmed by pathology,were not accept preoperative radiotherapy, and chemotherapy.2.Research methods: Using immunohistochemical SP method and RT-PCR(real-time quantitative- gathered more chain reaction semi-quantitative method for Realtime- polymerase chain reaction) technology to detect 25 cases of normal ovarian tissue, 25 cases of benign ovarian tumor tissue and 34 cases of epithelial ovarian cancer tissues Atg5, Beclin 1, and the expression of P53 protein and m RNA,combined with the clinical pathologic factors were analyzed.3. Statistical methods: Application SPSS18.0 statistical software to analysis the result of the experiment data, measurement data with said, using the single factor analysis of variance; Immunohistochemical results chi-square analysis application,using Pearson correlation analysis contingency, inspection level for alpha is 0.05.Results1.The expression of Atg5 m RNA in malignant and benign group and normal group are: 0.256, 0.514, 0.613; Atg5 protein in malignant and benign group and normal group respectively: the positive expression rate of 20.6%(7/34), 60%(15/25),88%(22/25). Atg5 m RNA and protein positive expression rate from the normal group, the expression of benign and malignant group in turn is reduced, The difference is statistically significant(P < 0.05).2.The expression of Beclin1 m RNA in malignant and benign group and normalgroup are: 0.234, 0.536, 0.624; Beclin1 protein in malignant and benign group and normal group respectively: the positive expression rate of 26%(9/34), 60%(15/25),92%(23/25). Beclin1 m RNA and protein positive expression rate from the normal group, the expression of benign and malignant group in turn is reduced, the differences were statistically significant(P < 0.05).3.The expression of P53 m RNA in malignant and benign group and normal group are: 0.843, 0.252, 0.236; P53 protein in malignant and benign group and normal group respectively: the positive expression rate of 76%(26/34), 12%(3/25),4%(1/25). P53 m RNA and protein positive expression rate expressed in malignant group was higher than the benign group and normal group, the difference is statistically significant(P < 0.05), and its expression differences in benign group and normal group has no statistical significance(P > 0.05).4.In epithelial ovarian cancer tissues, Atg5, Beclin1 and P53 protein expression related to patient’s clinical and pathological staging(P < 0.05), with the progress of the clinical and pathological staging, Atg5, the lower the Beclin1 protein expression and P53 protein expression is higher, and has nothing to do with the patient’s age,pathological type and lymph node metastases(P > 0.05).5. In epithelial ovarian cancer tissues, Atg5 and Beclin1 protein expression was positively correlated(r = 0.461 P < 0.05), P53 protein expression and Atg5, Beclin1 protein expression were negatively correlated(r = 0.495,P < 0.05 and r = 0.542, P <0.05).Conclusions1.The abnormally low expression of Beclinl and Atg5 in epithelial ovarian cancer may be involved in inhibition of epithelial ovarian cancer development.2.P53 in epithelial ovarian cancer tissue of the abnormal high expression increases, it may participate in epithelial ovarian cancer development.3.In ovarian cancer tissues, autophagy related genes Atg5 and Beclin1 expression were positively correlated, Atg5 and negatively correlated to theexpression of P53, Beclin1 and negatively correlated to the expression of P53,illustrate the three in the pathogenesis of epithelial ovarian sex synergy. |
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