Expession Of DAPK3 In Cervical Cancer And The Relationship To The Patients' Progonsis

BackgroundCervical Cancer is the most common gynecological malignancy in China.The incidence of cervical cancer is second only to breast cancer.According to the statistics of the National Cancer Center,there are 98 900 newly diagnosed and 30 500 deaths of cervical cancer in China in 2015.Globally,it is estimated that there are 52,9800 new cases and 275,100 deaths each year,of which about 80% are new cases and deaths.Born in developing countries,it seriously threatens the health of women.Cervical cancer is the second leading cause of mortality among women worldwide,and its incidence has tended to be younger in recent years.According to the existing diagnosis and treatment methods,the survival rate and late recurrence rate of cervical cancer are not optimistic.Cervical cancer is the second most common malignant tumor in the world,and its incidence tends to be younger in recent years.It is the fourth most common malignant tumor after breast cancer,colorectal cancer and lung cancer.According to data from American Cancer Society(ACS),there were 12820 new cases of cervical cancer in the United States in 2017,4210 deaths,and the International Federation of Obstetrics and Gynecology(International Federation of Obstetrics and Gynecology).The revised clinical staging TNM classification(8th edition)of nal Federation of Obstetrics and Gynecology(FIGO)is the standard staging of cervical cancer.DAPK3(death-associated protein kinase-3)gene is located on autosomal chromosome 1.Its coding proteins are a class of 46 KDa molecular weight proteins,which are serine/threonine protein kinases with apoptotic activity,mainly related to cell death.DAPK is mediated by promoter hypermethylation,self-phosphorylation of calcineurin binding region,protein inactivation and inhibition of DAPK phosphorylation sites.DAPK3 gene was inactivated.It has been confirmed that the DAPK family consists of five members: DAPK,DRP-1/DAPK2,D1K/ZIPK,DRAKl and DRAK2.Its structure includes multiple domains of N-terminal kinase domain,Ca2+/Ca M regulatory domain,anchor protein duplication,cytoskeleton binding domain and C-terminal death domain.Their core kinase domain and myosin light chain kinase are basically similar.Its structure consists of contact reaction center and non-contact reaction center.The contact reaction center is composed of the core kinase region and the calcium ion/calmodulin binding region,of which the calcium ion/calmodulin binding region is the most important component.The non-contact reaction center consists of one cytoskeleton binding region,one death region,two P-loop loops and eight.Anchor protein repeats and serine-rich tails make up 83% of the members of the family,but the dead regions at the C-terminal are different,which is thought to be related to the function of DAPK.Studies have shown that traditional methods of inactivation of tumor suppressor genes mainly include gene mutation and gene mutation.Different from traditional methods of inactivation of tumor suppressor genes such as P53,DAPK3 is silenced by abnormal methylation of promoter,which is called the "third way" of tumor gene inactivation.DAPK3 is usually expressed as a loss of expression rather than mutation in tumors.It is generally homologous and highly evolutionarily homologous in organisms,suggesting that DAPK3 may play an important biological role.Relevant literatures at home and abroad reported that in gastric cancer,cervical cancer,prostate cancer,non-small cell lung cancer,breast cancer,the expression of DPAK3 is down-regulated,and its expression level is related to the level of tissue differentiation and disease.Overexpression of DAPK3 may inhibit cell colony formation and promote cell apoptosis.These studies suggest that DAPK3 may be a new tumor suppressor gene and play a role in the occurrence,development and prognosis of tumors.According to recent studies,the pathogenesis of cervical cancer involves the expression disorder of multiple oncogenes and tumor suppressor genes.The imbalance between the activation of oncogenes and the inactivation of tumor suppressor genes and their interaction is the molecular basis of the occurrence and development of cervical cancer.In the process of transformation of cancer cells,the inactivation of the function of tumor suppressor genes plays a more crucial role than the activation of proto-oncogenes.Therefore,the identification of new cervical cancer-related tumor suppressor genes provides a new theoretical basis for elucidating the molecular mechanism of cervical cancer.objectiveIn this study,we examined the expression of DAPK3 protein in cervical cancer and its relationship with prognosis,to explore the role and significance of DAPK3 in the occurrence,development,metastasis and prognosis of cervical cancer,in order to provide clinical basis for the diagnosis and treatment of cervical cancer.Method1.Immunohistochemical SP method was used to detect the expression of DAPK3 protein in 192 cases of cervical cancer and 108 cases of normal cervical tissue.2.To analyze the relationship between the expression of DAPK3 protein and clinicopathological parameters of cervical cancer and its influence on the prognosis of cervical cancer.Result1.There were 119 cases of low expression(119/192,61.97%)and 73 cases of high expression(73/192,38.03%)in 192 cases of cervical cancer,19 cases of low expression(19/108,17.59%)and 89 cases of high expression(89/108,82.41%)in 108 cases of normal cervical tissues,and the expression of DAPK3 in cervical cancer tissues was significantly different from that in normal tissues(P=0.000).2.The expression of DAPK3 in cervical cancer patients of different ages(P=0.002),FIGO staging(P=0.031),lymph node metastasis(P=0.017),histological grade(P=0.000),and different pathological types(P=0.009)had significant differences,but there was no significant difference with other clinical and pathological characteristics.3.The average progression-free survival time was 37 months in the low-expression group and 52 months in the high-expression group.The progression-free survival time in the low-expression group was significantly less than that in the high-expression group(P=0.045).4.Univariate analysis showed that lymphatic metastasis(P=0.029),histological grade of G3(P=0.033),pathological type of adenocarcinoma(P=0.025),FIGO stage of IB2-IIA(P=0.030)were all risk factors affecting overall progression-free survival.5.Multivariate analysis showed that intraoperative pathological evidence of lymphatic metastasis(P=0.014)and low expression of DAPK3(P=0.006)were independent risk factors for predicting progression-free survival of patients with cervical cancer.conclusion1.The expression of DAPK3 in cervical cancer tissues and normal cervical tissues has statistical difference,and the expression of DAPK3 gene is closely related to patient's age,FIGO stage,lymph node metastasis,histological grade and pathological type,which may predict poor prognosis of cervical cancer,and can be used as a basis for clinical diagnosis and treatment decisions.2.The low expression of DAPK3 may be involved in the growth,invasion,metastasis of cervical cancer,and is closely related to the prognosis of patients.It is expected to provide a basis for the diagnosis of cervical cancer and a new therapeutic target.