Expression And Clinical Significance Of COX-2 Pathway Related Proteins WBP2 And IFITM3 In Patients With Adenomyosis And Dysmenorrhea

Background:Adenomyosis(AM),a benign disease that can arise as diffuse or focal growth,is characterized by the presence that endometrial glands and stromal cells invading the myometrium,and ectopic endometrium causes proliferation and hypertrophy of myofibroblasts.Adenomyosis seriously affects the physical and mental health of patients.In recent years,the incidence rate of adenomyosis has increased year by year.Dysmenorrhea caused by adenomyosis which is also the prominent reason for patients to seek medical treatment and receive hysterectomy,has caused great pain to patients and seriously affects the quality of life of patients.At present,many drugs can alleviate the dysmenorrhea symptoms of adenomyosis in the clinical setting,while the efficacy of drugs is mostly temporary and dysmenorrhea relapses soon after the drug is withdrawn.Hysterectomy,the radical treatment of adenomyosis,is not appropriate of patients of childbearing age with reproductive requirements.There is a complex pathological mechanism of adenomyosis and algomenorrhea caused by the disease.Cyclooxygenase-2(COX-2)may be an important factor causing the occurrence of adenomyosis and dysmenorrhea.In recent years,the general development of proteomics technology that has been generally available to the study of diseases has greatly promoted the identification and quantification of proteins in biological samples.Label-free quantitative proteomics is promising in analyzing the protein changes of diseases.This study aims to explore the expression of COX-2 pathway-related proteins(WBP2 and IFITM3)in adenomyosis through label-free quantitative proteomics and its relationship with clinical information such as dysmenorrhea in adenomyosis,and to provide potential targets for the treatment of algomenorrhea.Objective:To explore the expression of COX-2 pathway-related proteins,WBP2 and IFITM3,in adenomyosis.To analyze the relationship between COX-2,WBP2,IFITM3 and clinical data such as dysmenorrhea in adenomyosis.Methods:40 samples of ectopic endometrium and the clinical data of adenomyosis were collected.Immunohistochemistry(IHC)was used to detect the expression of COX-2 in ectopic lesions of adenomyosis,in which 5 cases of COX-2 low expression samples were selected to constitute COX-2-low-expression group and five cases of COX-2 high expression samples were selected to constitute COX-2-high-expression group.The differential proteins between two groups,identified by label-free quantitative proteomics,were analysed by bioinformatics tools.WW domain binding protein 2(WBP2)and interferon induced transmembrane protein 3(IFITM3),important COX-2 pathway related proteins,that can be involved in the occurrence and development of disease by participating in expression of many signal pathways,were selected as the research objects.The expression of WBP2 and IFITM3 in ectopic lesions of adenomyosis were detected by IHC,and the relationship between COX-2,WBP2,IFITM3 and clinical data such as dysmenorrhea were analysed.Results:1.COX-2 pathway-related proteins were significantly enriched in a variety of biological processes,such as cell proliferation,cell invasion,signal transduction,autoimmunity,coagulation,cell apoptosis,and so on.2.The expression of COX-2 and IFITM3 in ectopic endometrium of adenomyosis were positively correlated with the severity of dysmenorrhea(P<0.05),while the expression of WBP2 was not significantly correlated with the severity of dysmenorrhea(P>0.05).3.The expression of WBP2 and IFITM3 in ectopic lesions of adenomyosis were both positively correlated with COX-2(P<0.05).And the expression of WBP2 in ectopic endometrium was positively correlated with IFITM3(P<0.05).Conclusion:1.COX-2 pathway-related proteins may be involved in many biological processes of ectopic endometrial cells in adenomyosis,such as cell infiltration,cell invasion,signal transduction,and so on,through being involved in autoimmunerelated pathways,complement coagulation cascade,cancer-related pathways,apoptosis and energy metabolism,etc.2.COX-2,WBP2 and IFITM3 may be involved in the occurrence and development of adenomyosis.3.COX-2 and IFITM3,positively correlated with the severity of dysmenorrhea,can be potential specific targets for the treatment of adenomyosis patients with dysmenorrhea.