ZIP4 is a novel molecular marker for glioma

Yi Lin, Yong Chen, Yongzhi Wang, Jingxuan Yang, Vivian F. Zhu, Yulun Liu, Xiaobo Cui, Leon Chen, Wei Yan, Tao Jiang, Georgene W. Hergenroeder, Stephen A. Fletcher, Jonathan M. Levine, Dong H. Kim, Nitin Tandon, Jay Jiguang Zhu, Min Li

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

BackgroundDysregulated 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.MethodsThe 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).ResultsThe 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).ConclusionsDysregulated 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.

Original languageEnglish (US)
Pages (from-to)1008-1016
Number of pages9
JournalNeuro-oncology
Volume15
Issue number8
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Fingerprint

Glioma
Zinc
Neoplasms
Brain
Brain Neoplasms
Survival
Confidence Intervals
National Cancer Institute (U.S.)
Atlases
Homeostasis
Genome
zinc-binding protein
Genes

Keywords

  • biomarker
  • brain tumor
  • prognosis
  • survival
  • zinc transporter
  • ZIP4

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Lin, Y., Chen, Y., Wang, Y., Yang, J., Zhu, V. F., Liu, Y., ... Li, M. (2013). ZIP4 is a novel molecular marker for glioma. Neuro-oncology, 15(8), 1008-1016. https://doi.org/10.1093/neuonc/not042

ZIP4 is a novel molecular marker for glioma. / Lin, Yi; Chen, Yong; Wang, Yongzhi; Yang, Jingxuan; Zhu, Vivian F.; Liu, Yulun; Cui, Xiaobo; Chen, Leon; Yan, Wei; Jiang, Tao; Hergenroeder, Georgene W.; Fletcher, Stephen A.; Levine, Jonathan M.; Kim, Dong H.; Tandon, Nitin; Zhu, Jay Jiguang; Li, Min.

In: Neuro-oncology, Vol. 15, No. 8, 01.08.2013, p. 1008-1016.

Research output: Contribution to journalArticle

Lin, Y, Chen, Y, Wang, Y, Yang, J, Zhu, VF, Liu, Y, Cui, X, Chen, L, Yan, W, Jiang, T, Hergenroeder, GW, Fletcher, SA, Levine, JM, Kim, DH, Tandon, N, Zhu, JJ & Li, M 2013, 'ZIP4 is a novel molecular marker for glioma', Neuro-oncology, vol. 15, no. 8, pp. 1008-1016. https://doi.org/10.1093/neuonc/not042
Lin Y, Chen Y, Wang Y, Yang J, Zhu VF, Liu Y et al. ZIP4 is a novel molecular marker for glioma. Neuro-oncology. 2013 Aug 1;15(8):1008-1016. https://doi.org/10.1093/neuonc/not042
Lin, Yi ; Chen, Yong ; Wang, Yongzhi ; Yang, Jingxuan ; Zhu, Vivian F. ; Liu, Yulun ; Cui, Xiaobo ; Chen, Leon ; Yan, Wei ; Jiang, Tao ; Hergenroeder, Georgene W. ; Fletcher, Stephen A. ; Levine, Jonathan M. ; Kim, Dong H. ; Tandon, Nitin ; Zhu, Jay Jiguang ; Li, Min. / ZIP4 is a novel molecular marker for glioma. In: Neuro-oncology. 2013 ; Vol. 15, No. 8. pp. 1008-1016.
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abstract = "BackgroundDysregulated 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.MethodsThe 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).ResultsThe 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).ConclusionsDysregulated 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.",
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T1 - ZIP4 is a novel molecular marker for glioma

AU - Lin, Yi

AU - Chen, Yong

AU - Wang, Yongzhi

AU - Yang, Jingxuan

AU - Zhu, Vivian F.

AU - Liu, Yulun

AU - Cui, Xiaobo

AU - Chen, Leon

AU - Yan, Wei

AU - Jiang, Tao

AU - Hergenroeder, Georgene W.

AU - Fletcher, Stephen A.

AU - Levine, Jonathan M.

AU - Kim, Dong H.

AU - Tandon, Nitin

AU - Zhu, Jay Jiguang

AU - Li, Min

PY - 2013/8/1

Y1 - 2013/8/1

N2 - BackgroundDysregulated 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.MethodsThe 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).ResultsThe 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).ConclusionsDysregulated 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.

AB - BackgroundDysregulated 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.MethodsThe 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).ResultsThe 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).ConclusionsDysregulated 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.

KW - biomarker

KW - brain tumor

KW - prognosis

KW - survival

KW - zinc transporter

KW - ZIP4

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