Epigenetic silencing of KAZALD1 confers a better prognosis and is associated with malignant transformation/progression in glioma

被引：17
作者：
Wang, Hongjun [1 ]
Feng, Ying [2 ]
Bao, Zhaoshi [3 ,4 ]
Jiang, Chuanlu [1 ]
Yan, Wei [3 ,4 ]
Wang, Yongzhi [3 ,4 ]
Zhang, Chuanbao [3 ,4 ]
Liu, Yanwei [3 ,4 ]
Zhang, Quangeng [2 ]
Zhang, Wei [3 ,4 ]
Jiang, Chuanlu [1 ]
机构：
[1] Harbin Med Univ, Affiliated Hosp 2, Dept Neurosurg, Harbin 150086, Heilongjiang, Peoples R China
[2] Capital Med Univ, Insistute Basic Med Sci, Dept Immunol, Beijing 100069, Peoples R China
[3] Beijing Neurosurg Inst, Beijing 100050, Peoples R China
[4] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100050, Peoples R China
来源：
ONCOLOGY REPORTS | 2013年 / 30卷 / 05期
基金：
中国国家自然科学基金;
关键词：
hypomethylation; KAZALD1; glioma; prognosis; DNA METHYLATION; PRIMARY GLIOBLASTOMA; GENE-EXPRESSION; CLASSIFICATION; CANCER; BIOMARKER; DENTIN; CORE;
D O I：
10.3892/or.2013.2706
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
In order to more thoroughly analyze aberrant DNA methylation in glioma, we applied a large cohort methylation microarray including 119 glioma samples. Six genes, ADCY1, KAZALD1, KLF4, SLMAP, TETRAN and TP53INP1, were screened out through significance analysis of microarray (SAM), survival Cox-regression and certain other pre-set conditions. We focused on the KAZALD1 oncogene. KAZALD1, also known as IGFBP-rP10, belongs to the IGFBP family. We found that KAZALD1 was hypomethylated in high-grade glioma (anaplastic gliomas and glioblastomas) compared to low-grade glioma (astrocytoma, oligodendrocytoma and oligoastrocytoma) using methylation microarrays (P<0.001). Immunohistochemistry (IHC) of 91 glioma samples showed that the KAZALD1 expression scores of high-grade glioma samples were higher compared to the scores of low-grade gliomas (P<0.001). In high-grade gliomas, overall survival (OS) was shorter for patients with KAZALD1 hypomethylation or overexpression compared to those without. Decreased KAZALD1 expression in glioma inhibited cell proliferation and invasion both in vitro and in vivo. On the basis of these observations and the results from subset analysis, it is reason-able to conclude that KAZALD1 promoter hypomethylation is an important prognostic biomarker in glioma. KAZALD1 promotes glioma malignant progression through invasion and proliferation.
引用
收藏
页码：2089 / 2096
页数：8
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