title: Epigenetic silencing of KAZALD1 confers a better prognosis and is associated with malignant transformation/progression in glioma.
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.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Bao
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Liu
authors.forename: Quangeng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D055515:Cysteine-Rich Protein 61 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008297:Male; D051379:Mice; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4