title: ZIP4 is a novel molecular marker for glioma.
abstract: BACKGROUND
  Dysregulated zinc transport has been observed in many cancers. However, the status of zinc homeostasis and the expression profile of zinc transporters in brain and brain tumors have not been reported.
  
  
  METHODS
  The gene profiles of 14 zinc importers (ZIPs) and 10 zinc exporters (ZnTs) in patients with glioma were studied by investigating the association between the zinc transporters and brain tumor characteristics (tumor grade and overall survival time). Three independent cohorts were analyzed to cross-validate the findings: the Chinese Glioma Genome Atlas (CGCA) cohort (n = 186), the US National Cancer Institute Repository for Molecular Brain Neoplasia Data (REMBRANDT) cohort (n = 335), and The University of Texas (UT) cohort (n = 34).
  
  
  RESULTS
  The expression of ZIP3, 4, 8, 14, ZnT5, 6, and 7 were increased, and the expression of ZnT10 was decreased in grade IV gliomas, compared with grade II gliomas. Among all 24 zinc transporters, ZIP4 is most significantly associated with tumor grade and overall survival; this finding is consistent across 2 independent cohorts (CGCA and REMBRANDT) and is partially validated by the third cohort (UT). High ZIP4 expression was significantly associated with higher grade of gliomas and shorter overall survival (hazard ratio = 1.61, 95% confidence interval = 1.02-2.53, P = .040 in CGCA cohort; hazard ratio = 1.32, 95% confidence interval = 1.08-1.61, P = .007 in REMBRANDT cohort).
  
  
  CONCLUSIONS
  Dysregulated expression of zinc transporters is involved in the progression of gliomas. Our results suggest that ZIP4 may serve as a potential diagnostic and prognostic marker for gliomas.
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Yang
authors.forename: Vivian F
authors.initials: VF
authors.lastname: Zhu
authors.forename: Yulun
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cui
authors.forename: Leon
authors.initials: L
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Georgene W
authors.initials: GW
authors.lastname: Hergenroeder
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Fletcher
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Levine
authors.forename: Dong H
authors.initials: DH
authors.lastname: Kim
authors.forename: Nitin
authors.initials: N
authors.lastname: Tandon
authors.forename: Jay-Jiguang
authors.initials: JJ
authors.lastname: Zhu
authors.forename: Min
authors.initials: M
authors.lastname: Li
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D027682:Cation Transport Proteins; D012333:RNA, Messenger; C486791:SLC39A4 protein, human
keywords: ZIP4; biomarker; brain tumor; prognosis; survival; zinc transporter