title: Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients.
abstract: Gene signatures derived from cancer stem cells (CSCs) predict tumor recurrence for many forms of cancer. Here, we derived a gene signature for colorectal CSCs defined by high Wnt signaling activity, which in agreement with previous observations predicts poor prognosis. Surprisingly, however, we found that elevated expression of Wnt targets was actually associated with good prognosis, while patient tumors with low expression of Wnt target genes segregated with immature stem cell signatures. We discovered that several Wnt target genes, including ASCL2 and LGR5, become silenced by CpG island methylation during progression of tumorigenesis, and that their re-expression was associated with reduced tumor growth. Taken together, our data show that promoter methylation of Wnt target genes is a strong predictor for recurrence of colorectal cancer, and suggest that CSC gene signatures, rather than reflecting CSC numbers, may reflect differentiation status of the malignant tissue.
authors: Laboratory of Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
authors: Felipe
authors: F
authors: de Sousa E Melo
authors: Selcuk
authors: S
authors: Colak
authors: Joyce
authors: J
authors: Buikhuisen
authors: Jan
authors: J
authors: Koster
authors: Kate
authors: K
authors: Cameron
authors: Joan H
authors: JH
authors: de Jong
authors: Jurriaan B
authors: JB
authors: Tuynman
authors: Pramudita R
authors: PR
authors: Prasetyanti
authors: Evelyn
authors: E
authors: Fessler
authors: Saskia P
authors: SP
authors: van den Bergh
authors: Hans
authors: H
authors: Rodermond
authors: Evelien
authors: E
authors: Dekker
authors: Chris M
authors: CM
authors: van der Loos
authors: Steven T
authors: ST
authors: Pals
authors: Marc J
authors: MJ
authors: van de Vijver
authors: Rogier
authors: R
authors: Versteeg
authors: Dick J
authors: DJ
authors: Richel
authors: Louis
authors: L
authors: Vermeulen
authors: Jan Paul
authors: JP
authors: Medema
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D007422:Intestines / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins