Clinical Research Papers:

The prognostic value of the stem-like group in colorectal cancer using a panel of immunohistochemistry markers

Chee Wee Ong _, Pei Yi Chong, Darragh G. McArt, Jason Yongsheng Chan, Hwee Tong Tan, Alan Prem Kumar, Maxey C. M. Chung, Marie-Véronique Clément, Richie Soong, Sandra Van Schaeybroeck, David J. J. Waugh, Patrick G. Johnston, Philip D. Dunne and Manuel Salto-Tellez

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Oncotarget. 2015; 6:12763-12773. https://doi.org/10.18632/oncotarget.3497

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Chee Wee Ong1, Pei Yi Chong2, Darragh G. McArt1, Jason Yongsheng Chan8, Hwee Tong Tan6, Alan Prem Kumar2,3,4,5, Maxey C. M. Chung6, Marie-Véronique Clément6,7, Richie Soong2, Sandra Van Schaeybroeck1, David J. J. Waugh1, Patrick G. Johnston1, Philip D. Dunne1,*, Manuel Salto-Tellez1,*

1Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Northern Ireland

2Cancer Science Institute of Singapore, National University of Singapore, Singapore

3Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

4Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia, Australia

5Department of Biological Sciences, University of North Texas, Denton, Texas, United States of America

6Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

7National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore

8Department of Medical Oncology, National Cancer Centre Singapore, Singapore

*These authors have contributed equally to this work

Correspondence to:

Manuel Salto-Tellez, e-mail: [email protected]

Keywords: colorectal, carcinoma, biomarkers, cancer stem-cell, immunohistochemistry

Received: January 22, 2015     Accepted: March 07, 2015     Published: March 26, 2015


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.

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