The Clinical Significance Of UPA Gene Promoter Methylation And It’s Expression In Glioma

Obiective We determine Urokinase type plasminogen activator (uPA) gene promoter region Methylation status and expression in glioma by Methylation specific polymerase chain reaction method (MSP) and immunohistochemical staining semi-quantitative method (IHC).And use statistical methods to analyze the uPA promoter methylation status and protein expression, respectively, with gender, age, and the relationship of tumor pathology classification, and analyze the uPA promoter methylation and uPA protein expression the correlation between them.And discuss the role of uPA gene promoter methylation in the development of glioma and the uPA protein expression relations with glioma pathological level.DNA methylation in epigenetic mechanisms of malignant tumor cells and provide guidance for individualized treatment.Methods During the period of January 2013 to August 2014,the 54 cases of malignant glioma samples were collected at Department of Neurosurgery,Second Hospital of Lanzhou University.By the WHO (2007) classification and grading standard, using the method of methylation specific polymerase chain reaction polymer to detect uPA gene promoter region methylation status, the calculation of methylation in different grade gliomas, part-methylation and unmethylation.The use of streptomycin resistance biological peroxidase immunohistochemical staining (SP method), particles in the cytoplasm of palm red for uPA protein positive expression.Positive cells observed under optical microscope and dyeing depth within the field of vision on counting the number of positive cells, calculated positive cell percentage of the total number of cells, results scoring standard immune response integral method.By SPSS13.0 software to analyze the uPA gene promoter methylation and uPA protein expression and correlation of clinical data and pathological data.Results UPA gene promoter in 54 cases of glioma tissue specimens in Ⅱ, Ⅲ and Ⅳ grade glioma in the methylation rate is 72.2,38.9 and 16.7% respectively, the pathological level statistically significant difference between groups (P< 0.05).The methylation status in patients with sex, age and pathological types (organization) between each group had no statistical difference (P> 0.05);uPA protein levels in Ⅱ, Ⅲ and Ⅳ grade glioma in the positive expression rate is 72.2,77.8 and 94.4% respectively, the pathological level statistically significant difference between groups (P< 0.05), and its expression in patients with sex, age and pathological types (organization) between each group had no statistical difference (P> 0.05).The experiment showed that the uPA gene promoter region methylation rate is reduced with the increasing of the pathological grading of gliomas.The uPA protein expression level is increased with the increasing of pathological grading of glioma and.uPA in Ⅳ grade glioma gene promoter region methylation and negatively correlated with the uPA protein expression (rs=-0.233, P= 0.029).Conclusion1. The uPA gene promoter region methylation and negatively correlated with pathological grading gliomas, particularly in Ⅳ level of glioblastoma.The promoter methylation is related with glioma growth and invasion.2. Methylation of low levels may activate the uPA proteins or promote the uPA protein expression.3. The uPA and pathological grading gliomas were positively related to the level of protein expression related to appreciation malignant glioma.4. UPA gene promoter methylation lead to uPA which appear low protein expression in glioma.The uPA in Ⅳ grade glioma gene promoter methylation status and uPA protein expression showed a negative correlation between them.