ZIP4 is a novel molecular marker for glioma
ZIP4 is a novel molecular marker for glioma
复制标题
ZIP4 是神经胶质瘤的新型分子标记。
DOI：
10.1093/neuonc/not042
复制
发表时间：
2013-08-01
期刊：
影响因子：
15.9
通讯作者：
Li, Min
中科院分区：
文献类型：
--
作者：
Lin, Yi;Chen, Yong;Li, Min
在许多癌症中已经观察到锌转运失调。然而，锌稳态的状态和锌转运蛋白在脑和脑肿瘤中的表达谱尚未阐明。本研究通过对14例脑胶质瘤患者锌转运蛋白（ZIP）和10例锌转运蛋白（ZnTs）基因表达谱的研究，探讨锌转运蛋白与脑胶质瘤特征（肿瘤分级和总生存时间）的关系。分析了三个独立的队列以交叉验证研究结果：中国胶质瘤基因组图谱（CGCA）队列（n = 186），美国国家癌症研究所分子脑肿瘤数据库（伦勃朗）队列（n = 335）和德克萨斯大学（UT）队列（n = 34）。与II级胶质瘤相比，IV级胶质瘤中ZIP 3、4、8、14、ZnT 5、6、7的表达增加，ZnT 10的表达减少。在所有24种锌转运蛋白中，ZIP 4与肿瘤分级和总生存期相关性最显著;这一发现在2个独立队列（CGCA和伦勃朗）中一致，并在第三个队列（UT）中得到部分验证。高ZIP 4表达与胶质瘤的高级别和较短的总生存期显著相关（CGCA队列中的风险比= 1.61，95%置信区间= 1.02-2.53，P = 0.040;伦勃朗队列中的风险比= 1.32，95%置信区间= 1.08-1.61，P = 0.007）。锌转运蛋白表达失调参与胶质瘤的进展。我们的研究结果表明，ZIP 4可能作为一个潜在的诊断和预后胶质瘤的标志物。
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.