| Research background:Endometrial cancer is one of the most common malignant tumors in the female reproductive system,accounting for 20%-30%of malignant tumors.In recent years,the incidence of the disease has been rising gradually with a younger trend,and the mortality rate has been increasing year by year,which has brought great impact on women's physical and mental health.According to statistics,there were about 6,3230 new cases of endometrial cancer and 1 1350 deaths worldwide in 2018.It has been found that proto-oncogenes and tumor suppressor genes are involved in the process of endometrial cancer,but the specific molecular mechanisms for the occurrence and development of endometrial cancer in research at home and abroad are still unclear.Inhibitor of growth family memember 4(ING4)is a new type of tumor suppressor gene,which has been widely studied and reported in recent years.It is reported that ING4 can bind to p300 to activate p53 and induce the expression of p21 tumor suppressor,thereby regulating the cell cycle and inhibiting cell proliferation.A large number of studies have shown that ING4 gene is related to the occurrence and development of various tumors.For example,the expression of ING4 in human lung adenocarcinoma?breast cancer?prostate cancer and melanoma is significantly reduced.However,there are few reports about the role of ING4 in endometrioid carcinoma at home and abroad at present.Therefore,this study examined the expression of ING4-p53-p21 signaling pathway in endometrioid carcinoma.on the one hand,to explore the expression of ING4 on endometrial cancer;On the other hand,to detect the correlation of their expression in endometrial cancer,which provide a new marker for clinical prevention and treatment of endometrial cancer,and also provide a theoretical basis for guiding the targeted treatment of endometrial cancer.Objective:To study the expression of ING4,p53,p21 in normal endometrial tissues,dysplasia endometrial tissues and endometrial cancer tissues,and their relationship with clinicopathological features of endometrial cancer.To explore the role of ING4 signaling pathway in endometrial cancer,and to provide a theoretical basis for pathological diagnosis,prevention and targeted therapy of endometrial cancer.Methods:In this study,tissue chip technology and immunohistochemical method were used to detect the expression of ING4,p53 and p21 protein in normal endometrial tissues,dysplasia endometrial tissues and endometrial cancer tissues;at the same time,Western blot method was used to compare The protein expression levels of ING4,p53 and p21 in endometrial cancer tissues and normal endometrial tissues adjacent to the cancer;and analyze the relationship between the expression levels of each protein and the clinicopathological characteristics of endometrial carcinoma and its relevance with the degree of endometrial lesions.Results:1.The positive expression rate of ING4 in endometrioid carcinoma was 23.3%,which was significantly lower than the 53.3%in the atypical hyperplasia group and 95.0%in the normal endometrial group.The difference between the three groups was significant(?2=32.477,P<0.05);The positive rate of the low-differentiated endometrioid carcinoma group was significantly lower than that of the medium-differentiated and high-differentiated groups.With the increase of the depth of myometrial infiltration and the clinical pathological stage,the positive expression rate of ING4 gradually decreased,and the differences were statistically significant(P<0.05).2.The positive expression rate of p53 in endometrioid carcinoma was 63.3%,which was significantly higher than the 40.0%in the atypical hyperplasia group and 15.0%in the normal endometrial group.The difference between the three groups was statistically significant(?2=15.141,P<0.05);p53 expression was significantly different in endometrioid carcinoma tissues from patients with different histological grades,clinicopathological stages,and tumor myometrial invasion depth(P<0.05).3.The positive expression rate of p21 in endometrioid carcinoma was 28.3%,which was significantly lower than the 63.3%in the atypical hyperplasia group and 90.0%in the normal endometrial group.The difference between the three groups was statistically significant(?2=26.172,P<0.05);p21 expression was statistically significant in tissues of patients with endometrioid carcinoma with different histological grades,clinicopathological stages,and tumor muscle invasion depth(P<0.05).4.Western blot results showed that the expression levels of ING4 and p21 proteins in normal endometrial tissue adjacent to the cancer were significantly higher than those in endometrioid carcinoma(P<0.05),and the expression of p53 in endometrial cancer tissue was higher than that in cancer.Adjacent normal endometrium(P<0.05).5.The positive expression of ING4 and p21 in endometrioid carcinoma tissue was negatively correlated with the expression of p53;the positive expression of p21 was positively correlated with ING4.Conclusions:1.The The expression of ING4 and p21 was significantly reduced in endometrioid carcinoma;the expression of ING4,p53 and p21 was negatively correlated with the degree of differentiation and clinical stage of endometrioid carcinoma.2.The decreased expression of ING4 and p21 and the abnormal expression of p53 are involved in the development of endometrioid carcinoma.ING4 plays an important role in the regulation of cell cycle through p53 and p21 signaling pathways in endometrioid carcinoma,and can provide certain help for the early diagnosis and prognosis of endometrial cancer. |
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