| Research background:Ovarian cancer is the main cause of female death among gynecological malignancies in the world.Globally,nearly 230,000 women are diagnosed with epithelial ovarian cancer each year,and 150,000 of them die.At present,the cellular mechanism that regulates the progression of ovarian cancer is not fully understood.Ovarian epithelial malignant tumors are the most common type,including five core histological subtypes: high-grade serous,endometrioid,clear cell,low-grade serous and mucinous,each showing a different Molecular mechanism and clinical behavior.Ovarian serous carcinoma is the most common histological type.High-grade serous ovarian cancer accounts for nearly 60% of the total cases of epithelial ovarian cancer.It is the most aggressive subtype with a poor prognosis and low patient survival rate.Due to the lack of early diagnosis of ovarian cancer and the progress of chemotherapeutic drug resistance,the prognosis is poor,so there is an urgent need to find effective biomarkers and therapeutic targets.Inhibitor of growth family memember 4(ING4)is a candidate tumor suppressor gene.Related studies in vivo and in vitro have shown that ING4 is involved in cell cycle arrest,apoptosis,autophagy,contact inhibition,and hypoxia adaptation.Tumor angiogenesis,invasion and metastasis and other important tumor marker pathways.In addition,ING4 can also promote the sensitivity of cancer cells to chemotherapy and radiotherapy.Although the loss of ING4 protein has been observed in many types of cancer,there is increasing evidence that ING4 can be used in gene therapy.Wild-type p53 is a tumor suppressor gene.In most cancers,p53 will mutate and lose its tumor suppressor function.As a sentinel of stress factors,p53 protein regulates a series of key cellular processes,including cell cycle arrest and apoptosis.In various cancer types,ING4 interacts with p53.Studies have shown that ING4 induces the expression of p21/WAF1 by activating a promoter.p21/WAF1 is a p53 regulatory gene with clear characteristics,and its promoter contains a consistent sequence of p53 binding sites.In recent years,the research of ING4 protein in tumors has been increasing,but its related research in ovarian cancer is rare,especially in ovarian serous cancer.Ovary is an important endocrine organ for women,and various hormones have very precise synergy or antagonism.It has become a consensus that endocrine factors are the most important high-risk factor in the pathogenesis of ovarian cancer.As important sex hormones in women,estrogen and progesterone exert their biological effects through their respective receptors.Estrogen receptor(ER)and progesterone receptor(PR)are predictive and prognostic markers for malignant tumors in various endocrine organs,including endometrial cancer and breast cancer.Although its mechanism of action and its influence on the occurrence and development of epithelial ovarian tumors are not yet clear,endocrine therapy still provides new directions and ideas for the treatment of ovarian tumors.Objective:To study the expression of ING4 in ovarian serous cystadenoma,ovarian serous borderline tumor,and serous ovarian cancer,and its relationship with p53,p21,ER,PR.Combined with clinical data to explore their role in the occurrence and development of ovarian tumors and their relationship with clinicopathological characteristic.Methods:In this study,Tissue chip technology and immunohistochemical methods were used to detect the expression of ING4,p53,p21,ER and PR in 59 cases of serous ovarian cancer,20 cases of borderline serous cystadenoma,21 cases of serous cystadenoma.The relationship between the clinicopathological characteristics of serous ovarian cancer and its correlation with its expression in serous ovarian cancer.Results:1.The positive rates of ING4 in the ovarian serous carcinoma tissue group,borderline ovarian serous cystadenoma group and ovarian serous cystadenoma group were 3.39%,60%,95.24%,respectively.There was significant difference between the three groups(χ2=65.755,P<0.001).Two-by-two comparisons among the three groups: the positive expression rate of ING4 in the serous cystadenoma group was higher than that of the borderline ovarian serous cystadenoma group(P=0.09),and the positive expression rate of ING4 the borderline ovarian serous cystadenoma group was higher than that of the ovarian serous cystadenoma In the cancer group(χ2=32.829,P < 0.001),the positive expression rate of ING4 in the serous cystadenoma group was higher than the ovarian serous carcinoma group(χ2=65.532,P<0.01).2.The positive expression rate of wild-type p53 in the ovarian serous cancer tissue group,borderline serous cystadenoma group,and serous cystadenoma group were 55.93%,55.00%,and 90.48%,respectively.There is a difference between the three groups.Statistical significance(χ2=8.615,P=0.013).The positive expression rate of wild-type p53 in the serous cystadenoma group was higher than that in the ovarian serous carcinoma group,and the difference was statistically significant(χ2=8.124,P=0.04);the positive expression rate of wild-type p53 increased with that of ovarian serous carcinoma The degree of differentiation has an increasing trend(χ2=13.97,P=0.001),and a decreasing trend with the increase of pathological stage(χ2=1.52,P=0.01);the positive expression of wild-type p53 in cancer tissues with lymph node metastasis The rate was significantly reduced,and the differences were statistically significant.3.The positive rates of p21 in ovarian serous cancer tissue group,borderline ovarian serous cystadenoma group and ovarian serous cystadenoma group were42.37%,40%,and 90.48% respectively.Through statistical analysis,the three groups The difference was statistically significant(χ2=15.800,P < 0.001).Pairwise comparison between the three groups: the positive expression rate of the benign group was higher than that of the borderline ovarian serous cystadenoma group(χ2=11.607,P<0.001),and the borderline ovarian serous cystadenoma group was lower than that of the ovarian serous cystadenoma In the cancer group,the difference was not statistically significant,and the benign group was higher than the ovarian serous cancer group(χ2=14.480,P<0.001).4.The positive rates of ER in ovarian serous carcinoma tissue group,borderline ovarian serous cystadenoma group and ovarian serous cystadenoma group were38.98%,65%,and 80.95%,respectively.The difference between the three groups is statistically significant.Learning significance(χ2=12.397,P=0.002).Two-by-two comparisons between the three groups: the positive rate of the benign group was higher than that of the borderline ovarian serous cystadenoma group,the difference was not statistically significant;the positive rate of ER in the borderline ovarian serous cystadenoma group was higher than that of the ovarian serous carcinoma group(χ2=4.080,P=0.043);the positive rate of ER in the benign group was higher than that in the ovarian serous cancer group(χ2=10.912,P<0.001);the positive rate of ER was not significantly correlated with the severity of ovarian serous cancer.5.The positive rates of PR in the ovarian serous cancer tissue group,borderline ovarian serous cystadenoma group and ovarian serous cystadenoma group were8.47%,70%,and 85.71%,respectively.There are statistical differences between the three groups,academic significance(χ2=51.318,P=0.001).Two-by-two comparisons between the three groups: the positive rate of the benign group was higher than that of the borderline ovarian serous cystadenoma group,the difference was not statistically significant;the borderline ovarian serous cystadenoma group was higher than that of the ovarian serous carcinoma group(χ2=30.954,P<0.001);the positive rate of PR in the benign group was higher than that in the serous ovarian cancer group(χ2=45.107,P<0.001);the positive expression rate of PR has no significant correlation with the pathological stage,degree of differentiation and lymph node metastasis of ovarian serous carcinoma.Conclusions:1.In the ovarian serous cancer group ING4,the positive expression rate of wild-type p53 and p21 protein was significantly reduced,and the positive expression rate of wild-type p53 was correlated with lymph node metastasis in ovarian serous cancer;the positive expression rate of p21 protein varied with ovarian serous The increase of cancer pathological staging has a decreasing trend;and the positive expression rates of ING4 and p53 are positively correlated with p21,respectively,suggesting that the three may act on the occurrence and progression of OSC,and clarifying their mechanism of action can provide new clinical diagnosis and treatment for OSC.Ideas and methods.2.In the serous cystadenoma group,the positive expression rate of ER and PR was significantly higher than that of the ovarian serous carcinoma group.The positive expression rate of ER protein decreased with the increase of the pathological stage of ovarian serous carcinoma;the expression of ER and PR The condition can be used to judge the sensitivity of the tumor to hormones,which is helpful for endocrine therapy. |
