Preliminary Study On The Relationship Between ?2-microglobulin And Malignant Degree And Angiogenesis Of Glioma

Part One Study on the relationship between?2-microglobulin and malignant degree ofgliomas and survival of patientsObjective: To investigate the value of ?2-microglobulin differential expression in the diagnosis and treatment of glioma.Methods: Serum ?2-microglobulin concentration and clinicopathological data were collected from 203 cases of gliomas in Zhongnan Hospital of Wuhan University.The expression of ?2-microglobulin in 1134 glioma cases and clinicopathological data in TCGA database were also collected.The serum ?2-microglobulin concentration was measured by latex immunoturbidimetry in 203 patients with glioma at 2-3days before operation.The mutation status of gene IDH1 was detected by capillary electrophoresis in paraffin-embedded glioma tissues.In TCGA database,they determined the expression of ?2-microglobulin by RNA-Seq and the mutation status of IDH1 in tumors by single nucleotide polymorphism detection.Finally,the difference of ?2-microglobulin contene.And drawing the survival curve of Kaplan-Meier by the follow-up informatiot among glioma patients was compared with different WHO grade and different IDH1 mutation typn of patients with TCGA database show the relationship between the expression of ?2-microglobulin in gliomas and the prognosis of the patients.Results: The content of ?2-microglobulin in patients with WHO-IV glioma was significantly higher than that in other grades(WHO I-III)(p < 0.05).And the higher the grade of glioma,the higher the expression of ?2-microglobulin.In IDH1 wild type glioma,the content of ?2-microglobulin was significantly higher than that in mutant glioma(p < 0.05).Moreover,we got a result from Kaplan-Meier survival curve that the higher the expression of ?2-microglobulin in gliomas,the worse the survival time of patients with gliomas.Conclusion:The expression of ?2-microglobulin may play an important role inthe differentiation between WHO IV grade glioma and other grade glioma,as well as in the differentiation between IDH1 mutation and wild type.The expression of ?2microglobulin may play an important role in the differentiation between WHO IV grade glioma and other grade glioma,as well as in the differentiation between IDH1 mutation and wild type.And the higher ?2-microglobulin expression of gliomas may be with the higher the WHO grade and the shorter the survival time.Part Two Correlation between?2-microglobulin andVEGFA in gliomasObjective: To investigate the correlation between ?2-microglobulin and vascular endothelial growth factor A expression in glioma.Methods: The correlation analysis between the expression of all genes and?2-microglobulin in TCGA database was carried out.The strongly correlated genes were screened for gene ontology analysis and protein interaction network analysis.To find the correlation between the expression of ?2-microglobulin and vascular endothelial growth factor A.In order to verify the correlation between them,immunofluorescence semi-quantitative analysis about ?2-microglobulin and vascular endothelial growth factor A was performed on paraffin sections of 103 patients with glioma after operation.Results: The analysis of TCGA gene expression data showed that the genes positively related to ?2-microglobulin expression in glioma were mainly enriched in signal transduction,angiogenesis and regulation,positive regulation of NF-kappa B signal transduction and cell proliferation.The negative correlation genes were mainly enriched in chemical synaptic transmission and transmembrane movement.After protein interaction network analysis,it was found that the expression of?2-microglobulin in glioma was closely related to vascular endothelial growth factor(VEGF),a regulatory factor in the process of angiogenic regulation.Semi-quantitative analysis of paraffin section immunofluorescence showed that ?2-microglobulin wasfound in 38 cases of WHO IV glioblastoma.The positive rates of vascular endothelial growth factor A were 84.21% and 94.74%.Respectively,with the decrease of WHO grade of malignant glioma,the positive rates of the two proteins decreased.At the same time,the positive rates of ?2-microglobulin and vascular endothelial growth factor A in IDH1 wild type glioma were 85.96% and 89.47%.And the expression of?2-microglobulin was positively correlated with the expression of vascular endothelial growth factor A.Conclusion: In glioma,the increased expression of ?2-microglobulin may promote the growth and progression of tumor by inducing increased expression ofvascular endothelial growth factor-A,promoting angiogenesis and increasing vascular permeability in gliomas.