Reduced expression of a gene proliferation signature is associated with enhanced malignancy in colon cancer

A. Anjomshoaa, Y. H. Lin, M. A. Black, J. L. McCall, B. Humar, S. Song, R. Fukuzawa, H. S. Yoon, B. Holzmann, J. Friederichs, A. Van Rij, M. Thompson-Fawcett, A. E. Reeve

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The association between cell proliferation and the malignant potential of colon cancer is not well understood. Here, we evaluated this association using a colon-specific gene proliferation signature (GPS). The GPS was derived by combining gene expression data obtained from the analysis of a cancer cell line model and a published colon crypt profile. The GPS was overexpressed in both actively cycling cells in vitro and the proliferate compartment of colon crypts. K-means clustering was used to independantly stratify two cohorts of colon tumours into two groups with high and low GPS expression. Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (Plt;0.05), leading to shorter disease-free survival in both cohorts. This finding was not a result of methodological bias as we verified the well-established association between breast cancer malignancy and increased proliferation, by applying our GPS to public breast cancer data. In this study, we show that reduced proliferation is a biological feature characterizing the majority of aggressive colon cancers. This contrasts with many other carcinomas such as breast cancer. Investigating the reasons underlying this unusual observation may provide important insight into the biology of colon cancer progression and putative novel therapy options.

Original languageEnglish
Pages (from-to)966-973
Number of pages8
JournalBritish Journal of Cancer
Volume99
Issue number6
DOIs
StatePublished - 16 Sep 2008

Keywords

  • Colon cancer
  • Disease-free survival
  • Proliferation signature

Fingerprint

Dive into the research topics of 'Reduced expression of a gene proliferation signature is associated with enhanced malignancy in colon cancer'. Together they form a unique fingerprint.

Cite this