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Association Between CEP55 And PI3K/Akt/FoxM1 Signaling Pathway In Human Astrocytoma

Posted on:2018-02-09Degree:MasterType:Thesis
Country:ChinaCandidate:S S NieFull Text:PDF
GTID:2334330536463550Subject:Clinical pathology
Abstract/Summary:PDF Full Text Request
Objective: Astrocytoma originated from the neuroepithelial tissue is the most common tumor in the central nervous system of human being.astrocytoma accounts for about 61.4% of all neuroepithelial tumors.High invasion and poor prognosis is a typical feature of this tumor.Although we are currently taking the comprehensive treatment,including surgery,chemotherapy and radiotherapy to treat astrocytoma in clinical practice,it till can not be completely cured.Therefore,we still need to study the molecular mechanism of the occurrence and development of astrocytoma to seek new effective targets and treat therapeutic methods.Centrosomal protein 55(CEP55),as a highly coiled-coil protein,is an important component of regulation of cytokinesis in cell mitosis.However,in recent years,CEP55 protein has been found widely to be expressed in various human tumor tissues.Wang has demonstrated that CEP55 was also highly expressed in gliomas,and it is associated with tumor cell proliferation,apoptosis and glucose metabolism.However,whether the abnormal expression of CEP55 protein in gliomas is related to the invasion and metastasis of glioma cells has not been confirmed.FoxM1 is a member of the Forkhead family and is expressed mainly as a transcription factor in normal proliferating cells and tumor cells.In tumor cells,FoxM1 promotes tumors proliferation,invasion,angiogenesis,epithelialmesenchymal transition(EMT)through the regulation of PI3K/Akt,Raf/MEK/MAPK,Wnt and Hedgehog Signal pathway and other tumor-related factors such as p27,Skp2,MMP-2,VEGF and Smad3 etc.In addition,FoxM1 and CEP55 has also a certain correlation in oral squamous cell carcinoma.CEP55 has could increase the expression of FoxM1 protein and MMP-2protein,and thus promote tumor cells migration and invasion.Based on the previous researchs,this experiment's objective is to analyze the expression level of CEP55,p-Akt,FoxM1 and MMP-2 in astrocytoma from histopathology sapect and discuss the relationship between CEP55 and astrocytoma's biological characteristics.Methods:1 We used immunohistochemical ElivisionTM plus method to study the expression of CEP55,p-Akt,FoxM1 and MMP-2 in 81 diffuse astrocytoma(WHO grade ?),101 anaplastic astrocytoma(WHO grade ?),80glioblastoma(WHO grade ?)and 27 peritumoral brain tissue.In addition,we discussed the correlation analysis of four indexes and clinicopathological features.2 SPSS16.0 software was applicated.The experimental data were analyzed by Chi-square test and spearman correlation analysis.Results:1 The expression of CEP55 in peritumoral brain tissue and brain astrocytomaIn 262 cases of astrocytoma,CEP55 protein expression was positive in 170 cases,the positive rate was 64.9%(170/262).In the 27 cases of peritumoral brain tissue,CEP55 protein expression was positive only in 2 cases,the positive expression rate was 7.4%(2/27).The positive expression rate of CEP55 protein in astrocytic tumors was significantly higher than in peritumoral brain tissue(c(17)=33.562,P<0.05).The positive expression rates of CEP55 protein in diffuse astrocytoma,anaplastic astrocytoma and glioblastoma were 32.1%(26/81),75.2%(76/101)and 85.0%(68/80)respectively.The positive expression rate of CEP55 protein in anaplastic astrocytoma and in glioblastoma was higher than in diffuse astrocytoma(P<0.05),but there was no statistical difference between anaplastic astrocytoma and glioblastoma(P>0.05).2 The expression of p-Akt in peritumoral brain tissue and brain astrocytomaIn 262 cases of astrocytoma,the positive expression of p-Akt protein wasfound in 145 cases,the positive rate was 55.3%(145/262).In the 27 cases of peritumoral brain tissue,p-Akt protein expression positive was only 2 cases,the positive expression rate was 7.4%(2/27).The positive expression rate of p-Akt protein in astrocytoma was significantly higher than in peritumoral brain tissue(c(17)= 22.505,P<0.05).The positive expression rates of p-Akt protein in diffuse astrocytoma,anaplastic astrocytoma and glioblastoma were27.2%(29/81),58.4%(59/101)and 80%(64/80)respectively.Among them,the positive expression rate of p-Akt protein in anaplastic astrocytoma and in glioblastoma were higher than in diffuse astrocytoma(P<0.05),and the positive expression rate of p-Akt protein in glioblastoma was higher than in anaplastic astrocy-toma(P <0.05)3 The expression of FoxM1 in peritumoral brain tissue and brain astrocytomaIn 262 cases of astrocytoma,Fox M1 protein expression was positive in136 cases,the positive rate was 51.9%(136/262).And no positive expression of FoxM1 protein in 27 cases of peritumoral brain tissue.The positive expression rate of FoxM1 protein in astrocytoma was significantly higher than in peritumoral brain tissue(c(17)=26.473,P<0.05).The positive expression rates of FoxM1 protein in diffuse astrocytoma,anaplastic astrocytoma and glioblastoma were 16.0%(13/81),62.4%(63/101)and 75.0%(60/80)respectively.The positive expression rate of FoxM1 protein in anaplastic astrocytoma and in glioblastoma was higher than that in diffuse astrocytoma(P<0.05),but there was no statistical difference between anaplastic astrocytoma and glioblastoma(P>0.05).4 The expression of MMP-2 in peritumoral brain tissue and brain astrocytoma In 262 cases of astrocytoma,MMP-2 protein expression was positive in 156 cases,the positive rate was 59.5%(156/262).In the 27 cases of normal peritumoral tissue MMP-2 protein was positive only in 1 case,the positive expression rate was 3.7%(1/27).The positive expression rate of MMP-2 protein in astrocytoma was significantly higher than in peritumoral brain tissue(c(17)=30.758,P<0.05).The positive expression rates of MMP-2protein in diffuse astrocytoma,anaplastic astrocytoma and glioblastoma were23.5%(19/81),74.3%(75/101)and 77.5%(62/80)respectively.The positive expression rates of MMP-2 protein in anaplastic astrocytoma and glioblastoma were higher than in diffuse astrocytoma(P<0.05),but there was almost no difference between anaplastic astrocytoma and glioblastoma(P>0.05)5 Relationship between the expression of CEP55,p-Akt,FoxM1 and MMP-2 and clinical pathological characteristicsThe expression of CEP55,FoxM1 and MMP-2 in astrocytoma was positively correlated with the age of the patients(P<0.05),but not with the gender and tumor diameter(P>0.05).However,at all levels of astrocytoma,the three protin were not associated with age,gender,and tumor diameter(P>0.05).The positive rate of p-Akt protein expression in astrocytoma was not correlated with age,gender and tumor diameter(P>0.05).There was no correlation at all levels of astrocytoma.6 The relationship between CEP55 and p-Akt,FoxM1,MMP-2 protein expression in astrocytoma.Results showed that there is a positive correlation between CEP55 and p-Akt,FoxM1,MMP-2 at all levels of astrocytoma.(r=0.594,r=0.508,r=0.501,P<0.05);In diffuse astrocytoma there is a positive correlation between CEP55 and p-Akt,FoxM1,MMP-2(r=0.531,r=0.492,r=0.556,P<0.05);In anaplastic astrocytoma there is a positive correlation between CEP55 and p-Akt,FoxM1,MMP-2(r=0.494,r=0.312,r=0.240,P<0.05);In glioblastoma there also is a positive correlation between CEP55 and p-Akt,FoxM1,MMP-2(r=0.490,r=0.323,r=0.277,P<0.05).Conclusion:1 CEP55,p-Akt,FoxM1 and MMP-2 protein were overexpressed in human astrocytoma and that was associate with the tumorigenesis of astrocytoma.2 The expression of CEP55,FoxM1 and MMP-2 protein in anaplastic astrocytoma and glioblastoma was higher than in diffuse astrocytoma,suggesting that CEP55,FoxM1 and MMP-2 were involved in tumor cell differentiation.3 With the increase of astrocytoma's pathological grade,p-Akt protein positive expression significantly increased,suggesting that p-Akt be related to the development,differentiation and malignant process of astrocytoma.4 The expression of CEP55,FoxM1 and MMP-2 protein in astrocytoma was positively correlated with the age of the patients,and the expression of CEP55,FoxM1 and MMP-2 may increase with age.Thus,age may also be a influencing factor of astrocytoma.5 In astrocytoma the expression of CEP55 was positively correlated with p-Akt,FoxM1 and MMP2,suggesting that CEP55 has synergistic effect with p-Akt,FoxM1 and MMP2 to promote tumor cell aggressiveness.
Keywords/Search Tags:Astrocytoma, CEP55, p-Akt, FoxM1, MMP-2, Immunohistochemistry
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