GSE33113_eset.RdHigh expression of cancer stem cell (CSC) marker CD133 has been used as a predictor for prognosis in colorectal cancer (CRC), suggesting that enumeration of CSCs, using CD133, is predictive for disease progression. However, we showed recently that both CD133 mRNA and protein are not downregulated during differentiation of colon CSCs, pointing to an alternative reason for the prognostic value of CD133. We therefore set out to delineate the relation between CD133 expression and prognosis.A CRC patient series was studied for expression of CD133 and other CSC markers by microarray and quantitative PCR analysis. In addition, several common mutations were analyzed to determine the relation with CD133 expression.CD133 mRNA expression predicted relapse-free survival in our patient series, whereas several other CSC markers could not. Moreover, no correlation was found between expression of other CSC markers and CD133. Interestingly, high CD133 expression was related to mutations in K-Ras and B-Raf, and inhibition of mutant K-Ras or downstream mitogen-activated protein kinase kinase (MEK) signaling decreases CD133 expression. In addition, an activated K-Ras gene expression signature could predict CD133 expression in our patient set as well as data sets of other tumor types.CD133 expression is upregulated in CRC tumors that have a hyperactivated Ras-Raf-MEK-ERK pathway and is therefore related to mutations in K-Ras or B-Raf. As mutations in either gene have been related to poor prognosis, we conclude that CD133 expression is not indicative for CSC numbers but rather related to the mutation or activity status of the Ras-Raf pathway.
data( GSE33113_eset )
experimentData(eset):
Experiment data
Experimenter name: de Sousa E Melo F, Colak S, Buikhuisen J, Koster J et al.??Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients.??Cell Stem Cell??2011 Nov 4
Laboratory: Medema JP,??Tanis PJ 2011
Contact information:
Title: Mutations in the Ras-Raf Axis underlie the prognostic value of CD133 in colorectal cancer.
URL:
PMIDs: 22496204
Abstract: A 247 word abstract is available. Use 'abstract' method.
Information is available on: preprocessing
notes:
platform_title:
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
platform_shorttitle:
Affymetrix HG-U133Plus2
platform_summary:
hgu133plus2
platform_manufacturer:
Affymetrix
platform_distribution:
commercial
platform_accession:
GPL570
platform_technology:
in situ oligonucleotide
warnings:
No warnings yet
Preprocessing: frma
featureData(eset):
An object of class 'AnnotatedDataFrame'
featureNames: A1BG A1BG-AS1 ... ZZZ3 (19320 total)
varLabels: probeset gene
varMetadata: labelDescription
assayData: 19320 features, 96 samples
Platform type: hgu133plus2
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Available sample meta-data:
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alt_sample_name:
Length Class Mode
96 character character
sample_type:
adjacentnormal tumor
6 90
N:
0 NA's
90 6
M:
0 NA's
90 6
Dstage:
B NA's
90 6
age_at_initial_pathologic_diagnosis:
Min. 1st Qu. Median Mean 3rd Qu. Max. NA's
35.00 60.25 73.50 70.02 79.00 95.00 2
gender:
f m NA's
49 45 2
stageall:
2 NA's
90 6
days_to_recurrence_or_death:
Min. 1st Qu. Median Mean 3rd Qu. Max. NA's
50.0 508.8 1180.0 1234.0 1633.0 3599.0 2
batch:
Length Class Mode
96 character character
uncurated_author_metadata:
Length Class Mode
96 character character