The Expression Of Semaphorin3B Gene And Its Clinical Signaificance In Gliomas

Glioma, one of the most common tumors in the central nervous system, is derived fromthe neural epithelium and takes up more than40%of all the Brain tumors. Since itspathogenesis is not clear, the existing treatments are not effective to cure the disease. Andbecause tumors and normal brain tissues have no obvious boundaries, surgical removal ofthe tumors with radiotherapy and chemotherapy always leads to high rate of thepostoperative recurrence and short lifetime. Therefore, Glioma, one of the worst prognosistumors with high mortality among all neurosurgery diseases, has become one of the majorchallenges to be conquered by clinical doctors. The resent research has laid a solidfoundation for a better understanding of the pathogenesis of glioma, and earlier discovery oftumor markers, thus providing theoretical basis for individualized treatment of glioma.SEMA3B, a recently discovered candidate tumor suppressor gene, is located in21.3regionof Chromosome3short arm. SEMA3B belongs in Semaphorins protein family, a type ofsecretory protein with a variety of biological activity which involves in nerve cellregeneration, tumor formation, the cardiovascular morphology formation, the immuneresponse, nerve cells apoptosis, vascular endothelial cell migration etc. In the thesis,immunohistochemical and related clinical characteristics analysis is undertaken in69casesof glioma tissue and10cases of normal brain tissue both embedding wax block. VEGF,NRP1, and NRP2in normal brain tissues equally express weakly positive in one case whilein glioma their positive expression rate is74.00%(51/69),77.00%(53/69), and72.00%(50/69)respectively. The difference is statistically significant. In addition, the positive expression ofVEGF, NRP1, and NRP2in glioma of low grade (gradeâ… -â…¡) and high grade (gradeâ…¢-â…£)is69.00%(20/29),76.00%(22/29),72.00%(21/29) and80.00%(32/40),83.00%(33/40),78.00%(31/40) respectively, which suggests the positive expression is portioned to grade.The difference also is statistically significant. Through the DNA methylation analysis of43cases of gliomas and3cases of normal brain tissue, SEMA3B gene methylation frequencyis found out to be21/43(48.8%) and0%in normal tissue. Short arm of Chromosome3(3p)is the hotbed of tumor suppressor gene. SEMA3B gene is involved in DNA repair andapoptosis. Part of the promoter methylation may result in the decrease in expression, thus providing a selective advantage for the development of glioma and affecting apoptosis andmigration of the tumor cells. To define the gene methylation locus, pyrosequencing isundertaken in43cases of glioma and3cases of normal brain tissue. the density ofmethylation locus in SEMA3B gene promoter region in the glioma tissues is higher thanthat in the normal tissues. So methylation in SEMA3B gene promoter region may havetumor specificity and thus constitute the important molecular markers between glioma andnormal brain tissues. SEMA3B gene expression level in gliomas is portioned to the grade ofthe tumor.For better understanding of glioma, cultivate glioma cells in vitro, add Brucine and thenobserve the influence of Brucine on glioma cell apoptosis through QRT-PCT, MTT and flowcytometry. The results show that Brucine cuts the expression of COX-2and BCL-2mRNA,raises BAX mRNA expression, and inhibits glioma cell apoptosis. Therefore, Brucine maybe associated with glioma cell apoptosis. The research thus provides experimental supportfor further glioma cell research and clinical intervention.In summary, the tumor is a product of multi-genes and multi-factors which undergoesmore than one stages. For glioma treatment and prognosis, SEMA3B gene has become abreakthrough point.