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Expression And Correlation Of ASAH1,TGF Beta 1 And Caspase-3 In Human Gliomas

Posted on:2019-05-02Degree:MasterType:Thesis
Country:ChinaCandidate:X X QiaoFull Text:PDF
GTID:2404330566465305Subject:Surgery
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Objective:In primary intracranial malignancies,the proportion of gliomas is significant,and the degree of malignancy of gliomas is high.After comprehensive treatment such as surgery,radiotherapy,and chemotherapy,the recurrence rate is high and the survival period is short.With the development of molecular biology,the concept of treating gliomas from a molecular perspective has gradually become a new therapeutic direction.Acid Ceramidase(ASAH1)is one of the key enzymes in the metabolism balance system of sphingolipid(SPL)(an important component of the cell membrane),a type of ceramidase(CDase).With the increasing research on SPL in recent years,it has been found that SPL participates in signal transduction as a messenger in cellular biological activities.By regulating SPL metabolism,ASAH1 regulates many biological activities including apoptosis,immunity,stress,differentiation,and proliferation.The important role of ASAH1 in tumors occurring in various systems of the human body has also been gradually focused on and studied.Related studies have found that ASAH1 can inhibit the apoptosis of glioma cells,thereby promoting the development and progression of gliomas.Transforming growth factor ?1(TGF?1)signaling pathway is widely involved and has functions of regulating apoptosis,differentiation and proliferation.It has close relationship with ASAH1 in tumor progression and both have the effect of inhibiting cell apoptosis.It is related to the aspartate-specific caspase-3 signaling pathway.This study examined the expression of ASAH1,TGF?1,and Caspase-3 in gliomas to investigate the expression characteristics,correlation,and clinical significance of ASAH1,TGF?1,and Caspase-3 in glioma tissues with different pathological grades.Methods:From May 2015 to February 2017,70 cases of human glioma tissues were removed from neurosurgery at the Affiliated Hospital of Hebei University.All tissue specimens were fixed,embedded in paraffin,and sliced for later use.According to the classification of tumor gliomas of the central nervous system of WHO 2016,70 cases of glioma tissues were divided into high-grade group(WHO III-IV)and low-grade group(WHOI-II),of which I-II grade.In32 cases,18 cases were in grade III and 20 cases in grade IV.The expression of ASAH1,TGF?1,and Caspase-3 proteins in glioma tissues was detected by immunohistochemical SP method,and statistical methods were used to analyze the differences in expression of the three molecular indicators in the low and high-grade groups.The relationship between the survival time of patients with negative expression and the survival time of positive patients,and the relationship among the three indicators in glioma tissues.Results:The positive rates of ASAH1,TGF?1 and Caspase-3 expression in glioma tissue were81.42%,87.14% and 75.71%,respectively.1.The positive rates of ASAH1 expression in low-grade and high-grade glioma tissues were 68.75% and 92.10%,respectively,and the expression intensity was different.The expression intensity of ASAH1 in the high-grade group was significantly higher than that in the low-grade group(Z=-4.565).P=0.000).Patients with positive ASAH1 expression in selected cases had significantly shorter survival period(LogRank P=0.000)than patients with negative expression.2.The positive rates of TGF?1 expression in low-grade and high-grade glioma tissues were 81.25% and 92.10%,respectively,and the expression intensity was different.The expression of TGF?1 was significantly higher in the high-grade group than in the low-grade group(Z=-3.786 P=0.000).Patients with positive TGF?1 expression in selected cases had significantly shorter survival time than those with negative expression(LogRank P=0.002).3.The positive rates of Caspase-3 expression in low-grade and high-grade glioma tissues were 87.50% and 65.79%,respectively,and the expression intensity was different.The expression intensity of Caspase-3 in the high-grade group was significantly lower than that in the low-grade group(Z=-3.837 P=0.000).Patients with positive Caspase-3 expression in the selected case had significantly longer survival time than those with negative expression(LogRank P=0.000).There was a positive correlation between ASAH1 and TGF?1 expression(rs=0.652P=0.000).That is,with the up-regulation of ASAH1 expression in glioma tissues,TGF-?1expression was also enhanced.The expression of ASAH1 was negatively correlated with Caspase-3 expression(rs=-0.436 P=0.000).That is,as the expression of ASAH1 was increased in glioma tissues,the expression of Caspase-3 gradually decreased.TGF?1 was negatively correlated with the expression of Caspase-3(rs=-0.317 P=0.000).That is to say,with the increase of TGF?1 expression in glioma tissues,the expression of Caspase-3gradually decreased.Conclusion:1.The expression of ASAH1,TGF?1 and Caspase-3 in glioma is related to tumor grade,and is related to the survival and prognosis of patients.2.The expression of ASA1 and TGF?1 was positively correlated with the expression of Caspase-3 in gliomas.It was proved that ASAH1 was associated with tumor cell apoptosis and may be regulated by TGF?1.
Keywords/Search Tags:Glioma, Acid ceramidase, Transforming growth factor beta1, Caspase-3, Immunohistochemistry
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