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. 2015 May 20;6(14):12763-73.
doi: 10.18632/oncotarget.3497.

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

Chee Wee Ong  1 , Pei Yi Chong  2 , Darragh G McArt  1 , Jason Yongsheng Chan  3 , Hwee Tong Tan  4 , Alan Prem Kumar  2   5   6   7 , Maxey C M Chung  4 , Marie-Véronique Clément  4   8 , Richie Soong  2 , Sandra Van Schaeybroeck  1 , David J J Waugh  1 , Patrick G Johnston  1 , Philip D Dunne  1 , Manuel Salto-Tellez  1
Affiliations

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

Chee Wee Ong et al. Oncotarget. .

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.

Keywords: biomarkers; cancer stem-cell; carcinoma; colorectal; immunohistochemistry.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that no potential conflict of interests exists.

Figures

Figure 1
Figure 1. Unsupervised hierarchical clustering analysis of immunohistochemical staining profile
Heatmaps showing appearance of distinct patients clusters in Stage I a. II b. III c. and IV d. colorectal cancer cases.
Figure 2
Figure 2
Prognostic value of identified stem-like molecular sub-groups in a. Stage I and b. II colorectal cancer patients. The prognostic value of the stem-like classifier was also observed in c. Stage II patients who received no adjuvant treatment.
Figure 3
Figure 3. Representative immunohistochemistry images for the markers a. CD133, b. SOX2, c. OCT4, d. P27, e. P53 and f. COX-2
See this image and copyright information in PMC

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