title: The prognostic value of the stem-like group in colorectal cancer using a panel of immunohistochemistry markers.
abstract: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the Western world. It is becoming increasingly clear that CRC is a diverse disease, as exemplified by the identification of subgroups of CRC tumours that are driven by distinct biology. Recently, a number of studies have begun to define panels of diagnostically relevant markers to align patients into individual subgroups in an attempt to give information on prognosis and treatment response. We examined the immunohistochemical expression profile of 18 markers, each representing a putative role in cancer development, in 493 primary colorectal carcinomas using tissue microarrays. Through unsupervised clustering in stage II cancers, we identified two cluster groups that are broadly defined by inflammatory or immune-related factors (CD3, CD8, COX-2 and FOXP3) and stem-like factors (CD44, LGR5, SOX2, OCT4). The expression of the stem-like group markers was associated with a significantly worse prognosis compared to cases with lower expression. In addition, patients classified in the stem-like subgroup displayed a trend towards a benefit from adjuvant treatment. The biologically relevant and poor prognostic stem-like group could also be identified in early stage I cancers, suggesting a potential opportunity for the identification of aggressive tumors at a very early stage of the disease.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland.
authors.forename: Chee Wee
authors.initials: CW
authors.lastname: Ong
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Pei Yi
authors.initials: PY
authors.lastname: Chong
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland.
authors.forename: Darragh G
authors.initials: DG
authors.lastname: McArt
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Jason Yongsheng
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Hwee Tong
authors.initials: HT
authors.lastname: Tan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia, Australia.|Department of Biological Sciences, University of North Texas, Denton, Texas, United States of America.
authors.forename: Alan Prem
authors.initials: AP
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Maxey C M
authors.initials: MC
authors.lastname: Chung
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Marie-Véronique
authors.initials: MV
authors.lastname: Clément
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Van Schaeybroeck
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland.
authors.forename: David J J
authors.initials: DJ
authors.lastname: Waugh
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Johnston
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Dunne
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Salto-Tellez
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarkers; cancer stem-cell; carcinoma; colorectal; immunohistochemistry