Study On The Relationships Between Iron Metabolism,HMGB1 Expression And Ovarian Endometriosis

Background:Endometriosis(EMs)affects 10%-15% of women of childbearing age,and can occur in many organs,with ovarian EMs being the most common.As research progresses,it has been found that menstrual reflux-endometrial implantation may only be the origin of EMs.Changes in the pelvic microenvironment(iron excess,inflammatory factor,and estrogen and progesterone metabolic imbalances)have also been found to involve in the initiation and development of EMs and even malignant transformation.Countercurrent hemolysis or bleeding of ectopic lesions cause erythrocyte metabolites(free iron,hemosiderin,etc.)to accumulate in the pelvis and lead to oxidative stress,resulting in cell necrosis,imbalance of redox reactions,ineffective repair of DNA damage,proto carcinoma gene mutations.Ectopic endometrial cells and tissue fragments may be recognized as "pelvic foreign objects" to stimulate body alarm molecules,such as high mobility group box 1 protein(HMGB1),which binds to pathogen recognition receptors to initiate sterilize inflammation,promoting the production of oxidative stress and inflammatory factors.Therefore,erythrocyte metabolites(mainly iron metabolism index)and inflammatory mediators(HMGB1)may play a role in the onset and progression of ovarian EMs.Iron metabolism index and HMGB1 in humoral fluid of patients with ovarian EMs may be new clues in the initiation and development of this disease.Objective:By analyzing iron metabolism indexes(serum iron(SI),ferritin(FER),transferrin(TF),unsaturated iron-binding capacity(UIBC),total iron-binding capacity(TIBC),transferrin saturation(TS))and HMGB1 expression and by comparing their differences in ovarian EMs serum and cyst fluid,we aimed to explore its possible relevance with the initiation and development ovarian EMs.Methods:According to the inclusion and exclusion criteria formulated in this study,collected serum of 38 cases of ovarian EMs who were admitted to our gynecology department for the first time from November 2018 to December 2019 and were pathologically diagnosed as ovarian endometrial cysts;35 cases of benign ovarian tumors;28 cases of ovarian cancer;36 cases of health;15 cases of ovarian EMs cyst fluid.Automatic biochemical analyzer and enzyme-linked immunosorbent assay were used to detect the iron metabolism index and HMGB1 expression of each group,respectively.Results:1.Analysis of general clinical data of samples revealed: the age,menarche age,menstrual period,pregnancy and parity of the ovarian EMs group were statistically different from those of the ovarian cancer group,but opposite to those of the benign ovarian tumor group.2.Compared with the ovarian cancer group,the contents of SI,FER,TF,UIBC,and TIBC in ovarian EMs group were statistically different.The contents of SI,UIBC,and TS were statistically different from benign ovarian tumor group.In the ovarian EMs group,the contents of iron,FER,and TF in serum were statistically different from those in cyst fluid.3.The sensitivity,specificity,Youden index and AUC of combined analysis of all iron metabolism(serum iron,FER,TF,UIBC,TIBC,TS)indexes to differentiate ovarian EMs and ovarian cancer group was 85.7%,89.5%,75.2%,0.906,respectively.While in distinguishing ovarian EMs and benign ovarian tumor was 92.1%,51.4%,43.5%,0.757,respectively.4.Serum HMGB1 level in ovarian EMs group were statistically different from that in health group and ovarian EMs cyst fluid group.The serum HMGB1 level in benign ovarian tumor group was significantly different from that in the health group.The sensitivity,specificity,Youden index,AUC and cut-off value of HMGB1 to distinguish benign ovarian tumor from health group was 62.5%,92.9%,55.4%,0.827,13.01 ng/ml,respectively,P=0.000.The sensitivity,specificity,Youden index,AUC and cut-off value of of HMGB1 to differentiate ovarian EMs and health group was 64.3%,82.1%,46.4%,0.746,12.65 ng/ml,respectively,P = 0.002.Conclusion:1.The change of serum iron metabolism in ovarian EMs group is not obvious,suggesting that it may be related to the regulation of system iron metabolism.In the ovarian cancer group,FER was up-regulated and SI,UIBC,and TF were down-regulated,suggesting that tumor cells may involve in disturbing the balance of iron metabolism.Iron overload occurred in ectopic cysts of ovarian EMs,the iron metabolism indexes in cyst fluid may reflect the pathophysiological changes of chocolate cysts to a certain extent.2.The combined analysis of iron metabolism indexes(serum iron,FER,TF,UIBC,TIBC,TS)may be helpful in distinguishing ovarian EMs from benign ovarian tumors and ovarian cancer.3.HMGB1 can be used as a serological marker to help identify benign ovarian tumors and ovarian EMs patients with the health.