The Reduced ARL3 Expression Predictspoor Clinical Prognosis Of Glioma Patients

Introduction:Malignant glioma is the most common primary malignant brain tumor in adults with a poor prognosis.As a member of ARF subfamily of small GTPase superfamily,ARL3 plays a key role in regulating microtubule organization and protein trafficking and ARL3 has been identified to be involved in ciliary diseases affecting kidney and photoreceptor development.However,the pathophysiological functional role of ARL3 in cancer still remains unknown.In this study,we aimed to examine the expression level and prognostic value of ARL3 in glioma.In this study,we investigated the expression level of ARL3 in glioma samples by RT-PCR,immunohistochemistry and western blot.The relationship between ARL3 expression and glioma patient survival was investigated with different grade of clinical glioma samples.Furthermore,the predicative value of ARL3 expression in glioma patient survival was evaluated with the data collected from multiple datasets.The biological functions of ARL3 were studied by bioinformatics analysis using gene ontology(GO),and gene set enrichment(GSEA)analysis.ARL3 expression was down-regulated in glioma samples,and associated with tumor grade.Moreover,the high expression level of ARL3 was correlated with favorable prognosis in glioma.ARL3 strengthened the prognostic value of MGMT promoter methylation in GBM patients.In addition,GSEA analysis showed that immune-related risk signature was strongly correlated with low level of ARL3 expression in GBM.These results suggest a potential role of ARL3 as a prognostic marker and a therapeutic target for glioma patients.Methods:1.Tumor specimens and normal brain tissue samples from glioma patients at all levels were collected for RNA isolation and quantitative RT-PCR.2.Protein extraction and western blot analysis.3.Immunohistochemical staining.4.ARL3 expression and survival data mining.5.Statistical Analysis.Results:1.Compared with non-tumor tissues,the expression level of ARL3 in glioma specimens showed a trend of decrease(figure 1C,P = 0.0914).2.Patients with low ARL3 expression had a longer survival time than patients with high ARL3 expression(figure 2E,P = 0.0798).3.The survival time of patients with higher ARL3 expression level who accpet chemoradiotherapy was significantly longer than that patients with lower ARL3 expression level(figure 3C).4.The expression level of ARL3 in glioma patients with MGMT methylation was significantly higher than that in glioma patients without MGMT methylation(figure 3A).Conclusions:1.ARL3 expression decreased in glioma samples and was associated with tumor grade.2.High level of ARL3 expression was associated with favorable prognosis.3.ARL3,as a prognostic marker,has a potential role for GBM patients.