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

HONGJUN WANG, YING FENG, ZHAOSHI BAO, CHUANLU JIANG, WEI YAN, YONGZHI WANG, CHUANBAO ZHANG, YANWEI LIU, QUANGENG ZHANG, WEI ZHANG, CHUANLU JIANG
2013 Oncology Reports  
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 highgrade
more » ... ted in highgrade 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.
doi:10.3892/or.2013.2706 pmid:24002581 fatcat:ac43lhvgcngevcvdd7rq2ggeee