PMID- 23206951
OWN - NLM
STAT- MEDLINE
DCOM- 20130808
LR  - 20211021
IS  - 1755-8794 (Electronic)
IS  - 1755-8794 (Linking)
VI  - 5
DP  - 2012 Dec 4
TI  - Identification and characterization of alternative exon usage linked glioblastoma 
      multiforme survival.
PG  - 59
LID - 10.1186/1755-8794-5-59 [doi]
AB  - BACKGROUND: Alternative exon usage (AEU) is an important component of gene 
      regulation. Exon expression platforms allow the detection of associations between 
      AEU and phenotypes such as cancer. Numerous studies have identified associations 
      between gene expression and the brain cancer glioblastoma multiforme (GBM). The 
      few consistent gene expression biomarkers of GBM that have been reported may be 
      due to the limited consideration of AEU and the analytical approaches used. The 
      objectives of this study were to develop a model that accounts for the variations 
      in expression present between the exons within a gene and to identify AEU 
      biomarkers of GBM survival. METHODS: The expression of exons corresponding to 
      25,403 genes was related to the survival of 250 individuals diagnosed with GBM in 
      a training data set. Genes exhibiting AEU in the training data set were confirmed 
      in an independent validation data set of 78 patients. A hierarchical mixed model 
      that allows the consideration of covariation between exons within a gene and of 
      the effect of the epidemiological characteristics of the patients was developed 
      to identify associations between exon expression and patient survival. This 
      general model describes all three possible scenarios: multi-exon genes with and 
      without AEU, and single-exon genes. RESULTS: AEU associated with GBM survival was 
      identified on 2477 genes (P-value < 5.0E-04 or FDR-adjusted P-value < 0.05). 
      G-protein coupled receptor 98 (Gpr98) and epidermal growth factor (Egf) were 
      among the genes exhibiting AEU with 30 and 9 exons associated with GBM survival, 
      respectively. Pathways enriched among the AEU genes included focal adhesion, 
      ECM-receptor interaction, ABC transporters and pathways in cancer. In addition, 
      24 multi-exon genes without AEU and 8 single-exon genes were associated with GBM 
      survival (FDR-adjusted P-value < 0.05). CONCLUSIONS: The inferred patterns of AEU 
      were consistent with in silico AS models. The hierarchical model used offered a 
      flexible and simple way to interpret and identify associations between survival 
      that accommodates multi-exon genes with or without AEU and single exon genes. Our 
      results indicate that differential expression of AEU could be used as biomarker 
      for GBM and potentially other cancers.
FAU - Sadeque, Ahmed
AU  - Sadeque A
AD  - Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, 
      IL, USA.
FAU - Serao, Nicola Vl
AU  - Serao NV
FAU - Southey, Bruce R
AU  - Southey BR
FAU - Delfino, Kristin R
AU  - Delfino KR
FAU - Rodriguez-Zas, Sandra L
AU  - Rodriguez-Zas SL
LA  - eng
GR  - P30 DA018310/DA/NIDA NIH HHS/United States
GR  - R21DA027548/DA/NIDA NIH HHS/United States
GR  - P30DA018310/DA/NIDA NIH HHS/United States
GR  - 1R03CA143975/CA/NCI NIH HHS/United States
GR  - R03 CA143975/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121204
PL  - England
TA  - BMC Med Genomics
JT  - BMC medical genomics
JID - 101319628
RN  - 0 (ADGRV1 protein, human)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - *Alternative Splicing
MH  - Epidermal Growth Factor/genetics/metabolism
MH  - Exons
MH  - Female
MH  - Genome, Human
MH  - Glioblastoma/*genetics/mortality
MH  - Humans
MH  - Male
MH  - Models, Genetic
MH  - Odds Ratio
MH  - Oligonucleotide Array Sequence Analysis
MH  - Receptors, G-Protein-Coupled/genetics/metabolism
MH  - Survival Analysis
PMC - PMC3548711
EDAT- 2012/12/05 06:00
MHDA- 2013/08/09 06:00
PMCR- 2012/12/04
CRDT- 2012/12/05 06:00
PHST- 2012/07/06 00:00 [received]
PHST- 2012/11/27 00:00 [accepted]
PHST- 2012/12/05 06:00 [entrez]
PHST- 2012/12/05 06:00 [pubmed]
PHST- 2013/08/09 06:00 [medline]
PHST- 2012/12/04 00:00 [pmc-release]
AID - 1755-8794-5-59 [pii]
AID - 10.1186/1755-8794-5-59 [doi]
PST - epublish
SO  - BMC Med Genomics. 2012 Dec 4;5:59. doi: 10.1186/1755-8794-5-59.