Article

Multiplexed cell signaling analysis of metastatic and nonmetastatic colorectal cancer reveals COX2-EGFR signaling activation as a potential prognostic pathway biomarker.

Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20155, USA.
Clinical Colorectal Cancer (impact factor: 1.68). 05/2009; 8(2):110-7. DOI:10.3816/CCC.2009.n.018
Source: PubMed

ABSTRACT The identification of prognostic determinants of colorectal cancer (CRC), including prediction of occult metastasis, is of urgent consideration, based on the tremendous differences in outcome and survival between patients who present with metastasis or develop metastasis versus those patients with organ-confined or nonrecurrent disease. Currently, a great deal of attention has been focused on using gene expression profiles of tumor specimens as a launch point for prognostic biomarker discovery. In our study, we chose to focus on functional protein-based pathway biomarkers as a new information archive because it is these proteins that form the functional signaling networks that control cell growth, motility, apoptosis, survival, and differentiation. We used reverse-phase protein microarray analysis of laser capture microdissected CRC tumor specimens to profile broad cell signaling pathways from patients who presented with liver metastasis versus patients who remained recurrence free after follow-up. Our results indicate that members of the EGFR and COX2 signaling pathways appear differentially activated in the primary tumors of patients with synchronous metastatic disease. If validated in larger study sets, this pathway defect might be useful as a prognostic clinical tool as well as a guide to potential therapeutic intervention strategies that target occult disease and/or preventative measure.

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Keywords

colorectal cancer
 
control cell growth
 
COX2 signaling pathways
 
differentially activated
 
functional protein-based pathway biomarkers
 
functional signaling networks
 
gene expression profiles
 
larger study sets
 
launch point
 
liver metastasis
 
new information archive
 
nonrecurrent disease
 
occult metastasis
 
preventative measure
 
prognostic clinical tool
 
prognostic determinants
 
recurrence free
 
reverse-phase protein microarray analysis
 
synchronous metastatic disease
 
target occult disease