Detection Of Apoptosis Regulation Gene TRAIL, Caspase-3 And Survivin In Neuroblastoma And Its Significance

Background and Objective: Neuroblastoma is one of the most common pediatric solid tumors and derived from the sympathoad- renal lineage of the neural crest, the tumors frequently show spontaneous regression, which may involve apoptosis. It is now widespread to think, occurrence or not of cell apoptosis is a coefficient result of various factors, but that regulation of gene is a link of the very key of mechanism of apoptosis.TRAIL, Caspase-3, Survivin is now new-found several genes for promoting/ repressing apoptosis, among them TRAIL is a new member of the tumor necrosis factor super family( TNF), It is a kind of II type transmembrane protein, and can steadily express in almost all normal tissue, primarily and selectively induce the tumor cell apoptosis , but to the normal tissue almost have no any influence; TRAIL primarily binds its homologous receptors through its surface receptor binding sites, forms the components of DISC, and activates Caspase cascade, thereby induces cell apoptosis. Caspase-3 is a member of cysteine proteases family that is synthesized by pro-Caspase-3, and is located in the center of cell apoptosis path. TRAIL, Fas, TNF and otherwise factor can activate Caspase cascade, finally initiate the activating of Caspase-3 and induce cell apoptosis. Survivin is a novel member of the inhibitor of apoptosis proteins (IAP) family, it can positionicularily expresses in the tumor tissue, the embryo and the growth fetus tissue, but not in the terminally differentiated adult tissues (thymus, genital gland excepted). Survivincan block apoptosis by direct inhibition of activation of Caspase-3 or -7; in addition, it also cans indirect inhibition of them by p21 protein.As for expression and regulation mechanism of above three kinds of genes in the child neuroblastoma, current yet no be reported in our internal periodical. The purpose of this text is to study the value of these genes that occurrence, development, clinical diagnosis and prognostic distinguishing in child neuroblastoma, and provide a new direction of full of foreground for gene therapy of neuroblastoma.Methods: In this research the immunohistochemistory S-P method was adopted for detection of expression of Caspase-3 protein; TRAIL and Survivin mRNA expression were detected by in-situ hybrization technique, Single cell apoptosis was detected by TUNEL method. A p values less than 0.05 indicated statistical significance.Results:1) Comparing the difference of TRAIL expression among neuroblastoma, ganglioneuroblastoma and normal adrenmedullary tissue, indicates no statistical significance (p>0.05). Expression of TRAIL as well have no to show the statistical significance in some groups of neuroblastoma (p>0.05).2) Expression difference of Caspase-3 among three kinds of tissues, as well have no to show the statistical significance (p>0.05). Expression of Caspase-3 was connection with tissue type, clinical stage and histological classification factors in the neuroblastoma (p<0.05), and irrelevant to Age, sex and position factors (p>0.05).3) Expression level that Survivin in neuroblastoma is obvious higher than that in ganglioneuroblastoma and normal adrenmedullary tissue, difference between them have to show statistical significance (p<0.01); But no statistical significance was found for Survivin expression between other two tissues (p>0.05). Moreover, in neuroblastoma Survivin expression just was relation with age, clinical stage and histological classification (p O.001).4) No relativity was found between TRAIL mRNA and Caspase-3 proteinexpression in all of three kinds of tissues; Survivin mRNA was negative relation with Caspase-3 protein in neuroblastoma(r=-0.702, p=0.005); no relativity was found between them in other tissues. Finally Survivin expression was irrelevant to TRAIL expression in all of three kinds of tissues.5) No difference of expression of apoptosis index was found among three kinds of tissue (p>0.05); Only in tissue type, clinical stage and histological classification groups of...