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

Wang,Hongjun; Feng,Ying; Bao,Zhaoshi; Jiang,Chuanlu; Yan,Wei; Wang,Yongzhi; Zhang,Chuanbao; Liu,Yanwei; Zhang,Quangeng; Zhang,Wei; Jiang,Chuanlu

doi:10.3892/or.2013.2706

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

Authors:
- Hongjun Wang
- Ying Feng
- Zhaoshi Bao
- Chuanlu Jiang
- Wei Yan
- Yongzhi Wang
- Chuanbao Zhang
- Yanwei Liu
- Quangeng Zhang
- Wei Zhang
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Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Immunology, Insistute of Basic Medical Sciences, Capital Medical University, Beijing 100069, P.R. China, Beijing Neurosurgical Institute, Beijing 100050, P.R. China
Published online on: August 29, 2013 https://doi.org/10.3892/or.2013.2706
Pages: 2089-2096

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Abstract

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 reasonable to conclude that KAZALD1 promoter hypomethylation is an important prognostic biomarker in glioma. KAZALD1 promotes glioma malignant progression through invasion and proliferation.

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