Expressions Of DLX1, Foxm1, Smad4 And PAI-1 In Astrocytomas And Their Clinicopathological Significance

Objective:Astrocytoma is a group of astrocytic origin tumors that occurs predominantly in adults,and its biological behavior varies greatly.According to the latest molecular classification of CNS tumors(WHO 2016),finding new molecular targets has become a new direction for the treatment of astrocytomas.The homeobox gene DLX1(Distal-less Homebox 1)is involved in the regulation of embryonic development and cell differentiation.It could regulate the TGF-β/Smad4 pathway and promote tumor cell invasion and migration.In this experiment,immunohistochemistry(IHC)was used to compare the expression of DLX1 and related proteins in different grades of astrocytoma,and to explore its role and relationship with clinicopathological features and prognosis.Methods:The expression of FoxM1,DLX1,Smad4,and PAI-1 proteins were detected by immunohistochemistry in 86 cases of diffuse glioma(WHOII grade),102 cases of anaplastic astrocytoma(WHOIII grade)and 81 cases of glioblastoma(WHOIV grade).Further we investigated the above index proteins and their relationship with clinicopathological features and prognosis.Results:1.The positive expression rate of DLX1 protein was significantly high in astrocytomas compared to paraneoplastic brain tissue,but the positive expression rate was decreased following the increase of tumor grade(P<0.05).2.The positive expression rate of Smad4 protein was extremely low in astrocytomas compared to paraneoplastic brain tissue,and the positive expression rate gradually decreased following the increase of tumor grade(P<0.05).3.The positive expression rate of PAI-1 protein was higher in astrocytomas than that in paraneoplastic brain tissue.With the increase of tumor grade,the positive expression rate of PAI-1 protein was gradually increased(P<0.05).4.The positive expression rate of FoxM1 protein in astrocytoma was significantly higher than that in paraneoplastic brain tissue.With the increase of tumor grade,the positive expression rate of Fox M1 protein was gradually increased(P<0.05).5.The Fox M1 protein was weakly positively correlated with the patient’s tumor size(r=0.217).The Smad4 protein was negatively correlated with the patient’s tumor size(r=-0.421).FoxM1 and PAI-1 proteins were negatively correlated with the IDH1 mutation in patients(r=-0.245,r=-0.180).The Smad4 protein was weakly positively correlated with the IDH1 mutation in patients(r=0.209).6.Tumor grade,age,IDH1 mutation and tumor size were related to prognosis(P<0.05).Conclusion:1.The abnormal expression of DLX1,Smad4 and PAI-1 protein in astrocytoma of different grades suggests that the three were involved in the development of astrocytoma.2.DLX1 protein expression increased,Smad4 protein expression decreased,and its downstream protein PAI-1 increased expression,suggesting that DLX1 may promote the expression of PAI-1 through the TGF-β/Smad4 pathway and play an important role in the occurrence of astrocytoma effect.3.The Fox M1 protein was highly expressed and increased with increasing tumor grade,but was distinguished from DLX1,suggesting that it may not fully function through DLX1.4.The astrocytoma tumor grade,tumor size,presence of IDH1 mutations,and patient age were independent factors that influence prognosis.