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

doi:10.1093/neuonc/not042

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 journal › Article › peer-review

52 Scopus citations

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 language	English (US)
Pages (from-to)	1008-1016
Number of pages	9
Journal	Neuro-oncology
Volume	15
Issue number	8
DOIs	https://doi.org/10.1093/neuonc/not042
State	Published - Aug 2013
Externally published	Yes

Keywords

ZIP4
biomarker
brain tumor
prognosis
survival
zinc transporter

ASJC Scopus subject areas

Oncology
Clinical Neurology
Cancer Research

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10.1093/neuonc/not042

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@article{f861bb43c1e64ca1bdf9f248cb62c9a6,

title = "ZIP4 is a novel molecular marker for glioma",

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.",

keywords = "ZIP4, biomarker, brain tumor, prognosis, survival, zinc transporter",

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

year = "2013",

month = aug,

doi = "10.1093/neuonc/not042",

language = "English (US)",

volume = "15",

pages = "1008--1016",

journal = "Neuro-oncology",

issn = "1522-8517",

publisher = "Oxford University Press",

number = "8",

}

TY - JOUR

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

Y1 - 2013/8

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 - ZIP4

KW - biomarker

KW - brain tumor

KW - prognosis

KW - survival

KW - zinc transporter

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U2 - 10.1093/neuonc/not042

DO - 10.1093/neuonc/not042

M3 - Article

C2 - 23595627

AN - SCOPUS:84880646695

SN - 1522-8517

VL - 15

SP - 1008

EP - 1016

JO - Neuro-oncology

JF - Neuro-oncology

IS - 8

ER -

ZIP4 is a novel molecular marker for glioma

Abstract

Keywords

ASJC Scopus subject areas

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