| Human brain glioma is the most common endocranial primary tumor with high mortality and morbidity rates worldwide.The rate of incidence is 35.26%-60.96%(average 44.69%)according to national epidemiological statistics.It occurs in neuroectodermal,and its pathogenesis is unclear.The complexity of the central nervous system and neural network makes surgical intervention for neurosurgical disease somewhat complex.Glioma has a poor prognosis due to its rapid overgrowth,diffuse invasion,and chemotherapy resistance.It is divided into grade ? ~ ? by World Health Organization(WHO)(2007): 1.low-grade gliomas(Level? and Level?),which are common in children and young adults;2.high-grade gliomas(Level? and Level ?),which are common in the elderly.The improvements in clinical outcome are still limited and the identification of novel biomarkers involved in the progression of gliomas is still under critical demands.The prognosis of high-grade glioma(glioblastoma multiforme,GBM)remains gloomy mainly due to the low sensitivity to radio-/chemo-therapeutic agents,and tumor metastasis.The median survival of patients with GBM is still very short,about 14 months.Therefore,improved understanding of the mechanisms that involved in progression and metastasis of glioma is urgent essential to develop more effective therapies.The development of molecular biology to promote the progress of glioma is so rapid inrecent years,making molecular targeted therapy has become increasingly popular in the field of treatment of brain glioma.It can be predicted that the cure rate of glioma and median survival rates will be possible to obtain improved with more and more targeted drugs being found.Therefore,the analysis of the biological characteristics and exploring the associated pathogenesis of glioma from the genetic level has become the focus of most researches.B-cell translocation gene(BTG)family includes six proteins(BTG1 ?BTG2/PC3/Tis21?BTG3/Ana?BTG4/PC3B?TOB1and TOB2),which can suppress proliferation,cell cycle progression and induce differentiation.It is a new member of the family of antiproliferative genes.The down-regulated expression of BTG1 was detected in ovarian,esophageal squamous cell carcinoma,gastric cancer,hepatocellular carcinoma,thyroid carcinoma,lung and breast cancers.BTG1 can inhibit cell proliferation,metastasis,and angiogenesis and regulate cell cycle progression and differentiation in a variety of cell types,such as ovarian carcinomas.All of above proved BTG1 is a new tumor suppressor.Although these studies suggest BTG1 with tumor suppressor genes characteristic,whether BTG1 has the same effect in glioma? Its expression in gliomas has not been reported.Phosphatase and tensin homology deleted on chromosome 10(PTEN)is a tumor suppressor gene located on human chromosome 10 and plays a crucial role in the development and progression of tumor.It plays an important role in many tumors such as endometrial cancer,prostate cancer,renal cell carcinoma,colon cancer and lung cancer and so on.Studies have shown that PTEN inhibit the growth of brain glioma and a few studies try to find a new therapeutic target.In this study,the expression pattern of BTG1 and PTEN in the tissue of gliomas and normal brain tissue were detected,and the relationship of BTG1,PTEN,glioma grade of WHO and clinical application was analyzed,in order to clarify the roles of BTG1 and PTEN and provide a theoretical basis for the diagnosis and gene therapy for glioma.Materials and Methods1.80 cases of brain gliomas and 25 cases of normal brain tissue were collected from 2013-12 to 2016-4 in the first affiliated hospital of Zhengzhou University.2.Immunohistochemical En Vision was used to detect the expression of BTG1 protein and PTEN protein in 80 cases of brain gliomas and 25 cases of normal brain tissue.3.Western blot was used to test the expression of BTG1 protein and PTEN protein in 4 cases of fresh brain gliomas and 4 cases of fresh normal brain tissue.4.Statistical analysis: SPSS17.0 statistical software was used for statistical treatment.The data among groups were analyzed by Kruskal Wallis Test,Correlation by Spearman and Logistic analysis.All data were repeated for 3 times.The level of significant difference is ?=0.05?Results1.Immunohistochemical results:1.1.BTG1 protein was distributed to the cytoplasm,being light yellow,brown or tan.The positive rates of BTG1 protein in brain gliomas and normal brain tissue in the expression were 73.8%,96.0% respectively,the difference was statistically significant(P<0.05).The expression of BTG1 protein in glioma tissues was negatively related to grade of WHO(P<0.05),but its expression had nothing to do with the patient's sex and tumor size(P>0.05).1.2.PTEN protein was distributed to the cytoplasm,being light yellow,brown or tan.The positive rates of PTEN protein in brain gliomas and normal brain tissue were77.5%,100% respectively.It also had a statistically significant difference(P<0.05).The expression of PTEN protein in glioma tissues was negatively related to grade of WHO(P<0.05),but its expression had nothing to do with the patient's sex and tumor size(P>0.05).1.3.Expression of BTG1 and PTEN protein in gliomas and its relationship with clinicopathological parameters The relationship between the expression of BTG1 and PTEN protein and the grading of WHO gliomas revealed that there was a negative correlation between the expression of BTG1 and WHO grading(P <0.05).With the grade of tumor increased,the protein expression rate decreased and the intensity of expression decreased.The expression of BTG1 and PTEN in gliomas and normal brain tissues at each level were compared with each other(Kruskal Wallis Test analysis).The expression of BTG1 and PTEN in grade I gliomas and normal brain tissues were not significantly different(P> 0.05).There was no significant difference between grade ? and ?(P> 0.05).There were significant differences between the other groups(P< 0.05).The correlation analysis between BTG1 and PTEN(Spearman rank correlation test)showed a positive correlation between their expression.Logistic regression analysis showed that the expression of BTG1 and PTEN protein in patients over 20 years of age were lower than those of patients younger than 20 years(P <0.05).However,the expression of them was not related to tumor diameter and gender(P> 0.05).2.Western blot results:Western blot results were consistent with the results of immunohistochemistry.Conclusion1.BTG1 protein and PTEN protein play an important role in the process of development of gliomas.2.Testing of BTG1 protein and PTEN protein may provide additional reference for histology grade of glioma,and they may be new targets of gene therapy. |
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