Mutations in the Ras-Raf axis underlie the prognostic value of CD133 in colorectal cancer Full Text
Clinical Cancer Research, 04/12/2012
Kemper K et al. – 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 with 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.Methods
- A CRC patient series was studied for expression of CD133 and other CSC markers by microarray and qPCR analysis.
- Additionally, several common mutations were analyzed to determine the relation with CD133 expression.
- CD133 mRNA expression predicted relapse-free survival in our patient series, while 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 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 datasets of other tumor types.