The Expression And Clinical Significance Of Reactive Oxygen Species And Hypoxia Inducible Factor-1α In Ovarian Neoplasms

ObjectieThrough detectioning the expression of HIF-1alpha mRNA, protein and ROS inovarian cancer and benign ovarian epithelial tumor tissue,the aims of this study are todiscuss the relationship of clinicopathologic features of ovarian tumors, to explore therelationship between the expression of hypoxia inducible factor1alpha and the contents ofROS in ovarian cancer tissue,further to explore the abnormality of oxygen metabolismin epithelial ovarian carcinoma，and to explore the role in the development of ovariantumor.MethodsThe expression of HIF-1alpha mRNA and protein were detected by real time reversetranscription-polymerase chain reaction and immunohistochemical ElivisionTMplus twosteps.fluorescence microplate reader to detect the expression level of ROS in differenttissue cells.Results1.The relative content of HIF-1αmRNA was higher in the ovarian cancer group thanin benign cystadenomas group.(P=0.000).In benign ovarian tumors,early stage ofepithelial ovarian cancer group and advanced epithelial ovarian cancergroup,HIF-1αmRNA expression was significantly increased(P=0.000);In the group oflymph node metastasis,the expression of HIF-1αmRNA is more than the group of nolymph node metastasis(P=0.000); In the group of low differentiation,it is higher than thewell-differentiated group(P=0.000).2.HIF-1αprotein expression was localized in the plasma or nucleus of tumorcells,especially in the nucleus.The expression of HIF-lα was higher in malignant ovariantumors than in benign cystadenomas.There was obvious difference(P=0.005).In the late group,the positive rate(78.57%)was significantly higher than that of earlycase(33.33%)(P=0.000);In the group of lymph node metastasis,positive expression rate ofHIF-lαprotein was (76.67%),obviously higher than that without lymph nodemetastasis(51.52%)(P=0.038).3.The expression of ROS was higher in the ovarian cancer group than In benigncystadenomas group(p=0.000). In the group of lymph node metastasis,the expression ofROS is more than group of no lymph node metastasis(P=0.007); In the group of lowdifferentiation,it is higher than the well-differentiated group(P=0.000).In epithelial ovariancarcinoma,the expression of ROS was positively correlated with clinical stage andlymphatic metastasis and pathologic grade(high and low differentiation).4.There is a significantly positive correlation between the HIF-1α protein expressionand ROS(r=0.560，P=0.000); no correlation between the HIF-1α protein expression andROS in the group of high differentiation (r=0.251，P=0.410),but significantly positivecorrelation in the low differentiation (r=0.540，P=0.002); A highly linear correlation in thegroup of lymphatic metastasis(r=0.703，P=0.001), no correlation in the group of no lymphnode metastasis(r=0.288，P=0.700); no correlation between the HIF-1α protein expressionand ROS in the early group(r=0.439，P=0.057),but significantly positive correlation in theadvanced group (r=0.572， P=0.000); HIF-1αprotein expression and HIF-1αmRNAexpression also showed a positively correlation(r=0.839，P=0.000),but HIF-1αmRNAexpression and ROS(r=-0.376，P=0.002),Conclution1.In the epithelial ovarian cancer group,the expression of HIF-1alpha mRNA andHIF-1protein was significantly higher than that in benign ovarian epithelial tumor group;benign ovarian tumors, early stage epithelial ovarian carcinoma and advanced epithelialovarian cancer tissue， the HIF-1alpha mRNA and HIF-1protein expression wassignificantly increased, this is further evidence, hypoxia is the basic characteristics ofepithelial ovarian carcinoma, and with the progression of ovarian carcinoma, hypoxia wasgradually increased. that indicates that the expression of HIF-1alpha occurs mainly inpoor differentiation, the later stage and lymph node metastasis, tips that which is closelyrelated to potentially malignant biological behavior of epithelial ovarian cancer, and mayaffect the prognosis of epithelial ovarian carcinoma.2.The expression of ROS was higher in the epithelial ovarian carcinoma group thanIn benign cystadenomas group. IIn epithelial ovarian carcinoma,the expression of ROS was positively correlated with clinical stage and lymphatic metastasis and pathologic grade(high and low differentiation). It indicates that tumor cells in hypoxia condition, ROS andHIF-1alpha may be involved in the tumorigenesis process, ROS on the positive regulationof HIF-1a may play an important role in the invasion and metastasis process of ovarianepithelial carcinoma.3.In the group of epithelial ovarian cancer, HIF-1a mRNA and protein expressionwere increased, and the HIF-1expression of a protein and ROS were highly positive linearcorrelation. HIF-1mRNA and ROS showed a low correlation, which showed that inhypoxia condition, HIF-1a subunit on the oxygen dependence is strong, the modulationof ROS on the HIF-1a occurs at the transcriptional and protein levels, is mainly inprotein levels.