Methylation of Cancer-Stem-Cell-Associated Wnt Target Genes Predicts Poor Prognosis in Colorectal Cancer Patients

被引：279

作者：

de Sousa e Melo, Felipe ^{[1
]}

Colak, Selcuk ^{[1
]}

Buikhuisen, Joyce ^{[1
]}

Koster, Jan ^{[2
]}

Cameron, Kate ^{[1
]}

de Jong, Joan H. ^{[1
]}

Tuynman, Jurriaan B. ^{[1
]}

Prasetyanti, Pramudita R. ^{[1
]}

Fessler, Evelyn ^{[1
]}

van den Bergh, Saskia P. ^{[1
]}

Rodermond, Hans ^{[1
]}

Dekker, Evelien ^{[3
]}

van der Loos, Chris M. ^{[4
]}

Pals, Steven T. ^{[4
]}

van de Vijver, Marc J. ^{[4
]}

Versteeg, Rogier ^{[2
]}

Richel, Dick J. ^{[5
]}

Vermeulen, Louis ^{[1
]}

Medema, Jan Paul ^{[1
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Lab Expt Oncol & Radiobiol, Ctr Expt Mol Med, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands

[3] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands

[5] Univ Amsterdam, Acad Med Ctr, Dept Med Oncol, NL-1105 AZ Amsterdam, Netherlands

来源：

CELL STEM CELL | 2011年 / 9卷 / 05期

关键词：

COLON-CANCER; EXPRESSION SIGNATURE; BREAST-CANCER; PHENOTYPE; SPECIMENS; APC;

D O I：

10.1016/j.stem.2011.10.008

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：476 / 485

页数：10

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