Expression Of KDM4A In Breast Cancer Tissue And Its Relationship With Clinicopathological Features And Prognosis

Breast cancer is the most common malignancy in women in developed countries and the leading cause of cancer-related deaths among women worldwide.The incidence of breast cancer is highest in Western Europe and North America,and lowest in Africa and Asia.Thanks to advances in early screening and treatment,the mortality of breast cancer in Europe,especially in premenopausal women,has declined over the past decade and is also declining in the future.However,with the development of urbanization and the westernization of lifestyles,the incidence of breast cancer in lowand middle-income countries is rising.Since the 1990 s,the incidence of breast cancer has increased rapidly in China,which is more than twice the global growth rate.It has become the most common malignant tumor among urban women in China.At present,the main treatment methods for breast cancer are: surgical treatment,chemical medicine treatment,endocrine therapy and radiation therapy.The emergence of some targeted drugs such as trastuzumab has greatly prolonged the survival of patients with HER2+ breast cancer.However,in breast cancer with poor prognosis,such as triple-negative breast cancer,there is still high early metastasis and mortality.Therefore,it is important to find new targets for breast cancer treatment.Post-translational modification of histones is significant for gene expression in cells.Epigenetic modifications to histones include acetylation,methylation,ubiquitination,etc.,which alter chromatin structure and promote chromatin accessibility,leading to abnormal gene expression.Histone lysine demethylase 4A(Lysine(K)-specific demethylase 4A,KDM4 A,also known as JMJD2 A,JHD3A)is a histone demethylase that has been discovered in recent years.The methylation of the protein lysine affects the expression of genes at specific sites.In addition to demethylase-related effects,KDM4 A also exerts its protein-protein binding ability.By binding to specific proteins,it regulates gene expression.KDM4 A is widely expressed in various tissues of the human body,but the amount of expression is quite different.It is the lowest in skeletal muscle cells and the highest in lung tissue.KDM4 A is involved in some normal biological processes that have been found to affect embryo implantation and development in mice.KDM4 A has also been shown to be involved in tumor cell differentiation,proliferation,and cell cycle regulation.KDM4 A is highly expressed in various cancers such as bladder cancer,colon cancer,and endometrial cancer.This study used immunohistochemistry to detect the expression of KDM4 A in breast invasive ductal carcinoma,carcinoma in situ and paracancerous tissues,and to explore its relationship with clinicopathological features and prognosis in patients with invasive ductal carcinoma,to see whether KDM4 A is associated with breast cancer progression and clinicopathological features.METHODS: A total of 120 human breast cancer samples were collected,including 32 carcinomas in situ and 88 invasive ductal carcinomas.29 of the invasive breast cancer samples were matched with paracancerous tissues.The expression of KDM4 A in tissues was detected by immunohistochemistry,and the relationship between the expression of KDM4 A and clinicopathological features and prognosis was analyzed.RESULTS: KDM4 A was mainly expressed in the nucleus,and its expression in invasive ductal carcinoma was higher than that in the matched adjacent paracancerous tissues and carcinoma in situ.There was no significant difference in the expression of KDM4 A between carcinoma in situ and adjacent paracancerous tissues.In 88 cases of invasive ductal carcinoma,the number of KDM4 A high expression was 63(71.6%),compared with 14 cases(43.7%)of carcinoma in situ and 8 cases(27.6%)of adjacent paracancerous tissues the difference was statistically significant(P<0.05).There was no significant difference in the expression of KDM4 A between the carcinoma in situ and the adjacent tissues(X2=1.724,P=0.189).Chi-square test showed that KDM4 A expression was significantly associated with lymph node metastasis(P=0.001),distant metastasis(P=0.029),tumor grade(P=0.016),and HER2 status(P=0.011)in breast invasive ductal carcinoma.And has nothing to do with age,tumor size,ER,PR status.Survival analysis using Kaplan-Meier method and log-rank statistical test showed that the survival rate of KDM4 A high expression group in invasive ductal carcinoma was significantly lower than that in low expression group(P=0.019).Cox univariate analysis of factors associated with rate-related factors showed that high expression of KDM4 A was a risk factor for prognosis,but Cox multivariate regression analysis did not indicate that KDM4 A was an independent prognostic indicator.CONCLUSIONS: KDM4 A may be associated with breast cancer progression and is a risk factor for the prognosis of breast invasive ductal carcinoma.It may be used as an indicator to evaluate the prognosis of breast cancer patients and a potential therapeutic target.