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Abstract
Identification of gene expression changes that improve prediction of survival time across all glioma grades would be clinically useful. Four Affymetrix GeneChip datasets from the literature, containing data from 771 glioma samples representing all WHO grades and eight normal brain samples, were used in an ANOVA model to screen for transcript changes that correlated with grade. Observations were confirmed and extended using qPCR assays on RNA derived from 38 additional glioma samples and eight normal samples for which survival data were available. RNA levels of eight major mitotic spindle assembly checkpoint (SAC) genes (BUB1, BUB1B, BUB3, CENPE, MAD1L1, MAD2L1, CDC20, TTK) significantly correlated with glioma grade and six also significantly correlated with survival time. In particular, the level of BUB1B expression was highly correlated with survival time (p<0.0001), and significantly outperformed all other measured parameters, including two standards; WHO grade and MIB-1 (Ki-67) labeling index. Measurement of the expression levels of a small set of SAC genes may complement histological grade and other clinical parameters for predicting survival time.
Highlights
IntroductionIn a widely used measure, the level of Ki-67 protein is determined using an antibody called MIB-1 in a labeling index (MIB Li) that correlates with aggression and survival time in gliomas [6,7,8,9,10] and many other cancers [11,12,13,14,15,16]
Glioma tumors are the most common of central nervous system (CNS) neoplasms
In a widely used measure, the level of Ki-67 protein is determined using an antibody called MIB-1 in a labeling index (MIB Li) that correlates with aggression and survival time in gliomas [6,7,8,9,10] and many other cancers [11,12,13,14,15,16]
Summary
In a widely used measure, the level of Ki-67 protein is determined using an antibody called MIB-1 in a labeling index (MIB Li) that correlates with aggression and survival time in gliomas [6,7,8,9,10] and many other cancers [11,12,13,14,15,16]. One report indicated that RNA expression of Ki-67 correlated with survival time better than the antibody test, MIB Li, in colorectal carcinoma [17]. We looked at glioma grades II, III, and IV to uncover additional genes whose RNA expression correlated with grade and survival time. We used the statistical analysis suite WebArrayDB (http://www.WebArrayDB.org) [18] to analyze available microarray datasets of glioma RNA expression from various platforms that had already been used to identify hundreds of significant correlations of RNA levels with increasing glioma grade [19,20,21], including data stored at the Cancer Genome Anatomy Project (http://cgap.nci.nih.gov/Genes)
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