Expression Profile Analysis of Zinc Transporters (ZIP4, ZIP9, ZIP11, ZnT9) in Gliomas and their Correlation with IDH1 Mutation Status

Background: Zinc transporters have been considered as essential regulators in many cancers; however, theirmechanisms remain unknown, especially in gliomas. Isocitrate dehydrogenase 1(IDH1) mutation is crucial toglioma. This study aimed to investigate whether zinc transporters are correlated with glioma grade and IDH1mutation status. Materials and
Methods: IDH1 mutation status and mRNA expression of four zinc transporters(ZIP4, ZIP9, ZIP11, and ZnT9) were determined by subjecting a panel of 74 glioma tissue samples to quantitativereal-time PCR and pyrosequencing. The correlations between the expression levels of these zinc transportergenes and the grade of glioma, as well as IDH1 mutation status, were investigated.
Results: Among the four zinctransporter genes, high ZIP4 expression and low ZIP11 expression were significantly associated with higher grade(grades III and IV) tumors compared with lower grade (grades I and II) counterparts (p<0.0001). However,only ZIP11 exhibited weak correlation with IDH1 mutation status (p=0.045). Samples with mutations in IDH1displayed higher ZIP11 expression than those without IDH1 mutations.
Conclusions: This finding indicated thatzinc transporters may interact with IDH1 mutation by direct modulation or action in some shared pathwaysor genes to promote the development of glioma. Zinc transporters may play an important role in glioma. ZIP4and ZIP11 are promising molecular diagnostic markers and novel therapeutic targets. Nevertheless, the detailedbiological function of zinc transporters and the mechanism of the potential interaction between ZIP11 and IDH1mutation in gliomagenesis should be further investigated.