STANDARD_NAME	YAMANAKA_GLIOBLASTOMA_SURVIVAL_DN
SYSTEMATIC_NAME	M1948
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/YAMANAKA_GLIOBLASTOMA_SURVIVAL_DN
NAMESPACE	HUMAN_SEQ_ACCESSION
DESCRIPTION_BRIEF	Genes whose expression most strongly and consistently associated with the short term survival of patients with high grade glioma tumors.
DESCRIPTION_FULL	Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes coupled with a class prediction model could be used to define subgroups of high-grade gliomas in a more objective manner than standard pathology. RNAs from 29 malignant gliomas were analysed using Agilent microarrays. We identified 21 genes whose expression was most strongly and consistently related to patient survival based on univariate proportional hazards models. In six out of 10 genes, changes in gene expression were validated by quantitative real-time PCR. After adjusting for clinical covariates based on a multivariate analysis, we finally obtained a statistical significance level for DDR1 (discoidin domain receptor family, member 1), DYRK3 (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 3) and KSP37 (Ksp37 protein). In independent samples, it was confirmed that DDR1 protein expression was also correlated to the prognosis of glioma patients detected by immunohistochemical staining. Furthermore, we analysed the efficacy of the short interfering RNA (siRNA)-mediated inhibition of DDR1 mRNA synthesis in glioma cell lines. Cell proliferation and invasion were significantly suppressed by siRNA against DDR1. Thus, DDR1 can be a novel molecular target of therapy as well as an important predictive marker for survival in patients with glioma. Our method was effective at classifying high-grade gliomas objectively, and provided a more accurate predictor of prognosis than histological grading.
PMID	16652150
GEOID	
AUTHORS	Yamanaka R,Arao T,Yajima N,Tsuchiya N,Homma J,Tanaka R,Sano M,Oide A,Sekijima M,Nishio K
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 3: hazard ratio > 1
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AA404652,AF231512,AL137662,BAB22510,BC005861,BE045190,N92498,U20362,Y10183
GENE_SYMBOLS	IRF9,,NRBP2,TMEM218,ITGB2,DDR1,PDCD4,IFT88,ALCAM
FOUNDER_NAMES