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Gene expression profiling reveals Ki-67 associated proliferation signature in human glioblastoma / 中华医学杂志(英文版)
Chinese Medical Journal ; (24): 2584-2588, 2011.
Article in English | WPRIM | ID: wpr-292840
ABSTRACT
<p><b>BACKGROUND</b>Everlasting cellular proliferation is the fundamental feature during gliomagenesis and Ki-67 is one of the classical proliferation markers in human glioblastoma multiforme (GBM). However, the driver genes or core pathways for cellular proliferation in GBM have not been elucidated systematically.</p><p><b>METHODS</b>We evaluated by immunohistochemistry the prognostic value of Ki-67 expression in the clinical outcome of 156 Chinese patients with GBM and a total of 64 GBM samples were selected for further Agilent genome-wide microarray analysis. On the basis of the microarray data from Tiantan (n = 64) and The Cancer Genome Atlas (TCGA) (n = 202) database, differentially expressed genes between the GBM subgroups with high or low level of Ki-67 expression were identified using Significance Analysis of Microarrays (SAM). Gene Ontology (GO) and KEGG Pathway analyses were then undertaken for the Ki-67 associated genes to identify the most significant biological processes and signaling pathways.</p><p><b>RESULTS</b>We confirmed that Ki-67 was an independent prognostic indicator in the largest Chinese patient cohort of 156 GBM samples via immunohistochemical staining. Survival analysis of Ki-67 over-expression revealed a highly significant association with a worse clinical outcome (P = 0.010 for progression-free survival; P = 0.007 for overall survival). Comparative and integrated analysis between Tiantan and TCGA database identified a 247-gene "proliferation signature" (205 up-regulated and 42 down-regulated genes) that distinguished Ki-67 expression phenotypes. GO and KEGG Pathway analyses further indicated that Ki-67 expression phenotype was associated with distinct changes in gene expression associated with the regulation of cellular growth and proliferation.</p><p><b>CONCLUSIONS</b>Proliferation marker Ki-67 is an independent prognostic indicator in Chinese GBM patients. And Ki-67 associated proliferation signature identified through genome-wide microarray analysis may provide potential targets for anti-proliferation therapy in GBM.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: In Vitro Techniques / Immunohistochemistry / Glioblastoma / Ki-67 Antigen / Computational Biology / Oligonucleotide Array Sequence Analysis / Gene Expression Profiling / Cell Proliferation / Genetics / Metabolism Limits: Humans Language: English Journal: Chinese Medical Journal Year: 2011 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: In Vitro Techniques / Immunohistochemistry / Glioblastoma / Ki-67 Antigen / Computational Biology / Oligonucleotide Array Sequence Analysis / Gene Expression Profiling / Cell Proliferation / Genetics / Metabolism Limits: Humans Language: English Journal: Chinese Medical Journal Year: 2011 Type: Article