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Title: Hypoxia driven gene expression is an independent prognostic factor in stage II and III colon cancer patients
Authors: Dekervel, Jeroen ×
Hompes, Daphne
van Malenstein, Hannah
Popovic, Dusan
Sagaert, Xavier
De Moor, Bart
Van Cutsem, Eric
D'Hoore, André
Verslype, Chris
van Pelt, Jos #
Issue Date: Apr-2014
Publisher: Association for Cancer Research
Series Title: Clinical Cancer Research vol:20 issue:8 pages:2159-2168
Abstract: Purpose - Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients. Experimental design - Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray data sets. These data sets were further used to downsize and optimize a gene score, which was subsequently determined in paraffin embedded material of 126 patients with colon cancer treated in our center. Results - In the CaCo-2 cells, 923 genes with a 2-fold change and Limma corrected p≤0.0001 were found differentially expressed in hypoxia versus normoxia. We identified 21 genes with prognostic value and overlapping in three different training sets and (n=224). With a fourth published data set (n=177), the six gene Colon Cancer Hypoxia Score (CCHS) was developed. Patients with low CCHS showed a significant better disease free survival at three years (77.3%) compared to high CCHS patients (46.4%) (Log rank, p=0.006). This was independently confirmed in an external patient cohort of 90 stage II patients (86.9% vs 52.2%, p=0.001). Conclusions - Hypoxia driven gene expression is associated with high recurrence rates in stage II and III colon cancer. A 6-gene score was found to be of independent prognostic value in these patients. Our findings require further validation and incorporation in the current knowledgee on molecular classification of colon cancer.
URI: 
ISSN: 1078-0432
Publication status: published
KU Leuven publication type: IT
Appears in Collections:ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Hepatology
Abdominal Surgical Oncology
Department of Health and Technology - UC Leuven
Translational Cell & Tissue Research
Clinical Digestive Oncology (+)
Surgical Oncology
× corresponding author
# (joint) last author

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