title: Reduced expression of a gene proliferation signature is associated with enhanced malignancy in colon cancer.
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 (P < 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.
authors.affiliation: Department of Biochemistry and Cancer Genetics Laboratory, University of Otago, Dunedin, New Zealand.
authors.forename: A
authors.initials: A
authors.lastname: Anjomshoaa
authors.forename: Y-H
authors.initials: YH
authors.lastname: Lin
authors.forename: M A
authors.initials: MA
authors.lastname: Black
authors.forename: J L
authors.initials: JL
authors.lastname: McCall
authors.forename: B
authors.initials: B
authors.lastname: Humar
authors.forename: S
authors.initials: S
authors.lastname: Song
authors.forename: R
authors.initials: R
authors.lastname: Fukuzawa
authors.forename: H-S
authors.initials: HS
authors.lastname: Yoon
authors.forename: B
authors.initials: B
authors.lastname: Holzmann
authors.forename: J
authors.initials: J
authors.lastname: Friederichs
authors.forename: A
authors.initials: A
authors.lastname: van Rij
authors.forename: M
authors.initials: M
authors.lastname: Thompson-Fawcett
authors.forename: A E
authors.initials: AE
authors.lastname: Reeve
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D015331:Cohort Studies; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger