title: Multiplexed cell signaling analysis of metastatic and nonmetastatic colorectal cancer reveals COX2-EGFR signaling activation as a potential prognostic pathway biomarker.
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.
authors.affiliation: Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20155, USA.
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Pierobon
authors.forename: Valerie
authors.initials: V
authors.lastname: Calvert
authors.forename: Claudio
authors.initials: C
authors.lastname: Belluco
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
authors.forename: Jianghong
authors.initials: J
authors.lastname: Deng
authors.forename: Mario
authors.initials: M
authors.lastname: Lise
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Enzo
authors.initials: E
authors.lastname: Mammano
authors.forename: Francesco
authors.initials: F
authors.lastname: De Marchi
authors.forename: Lance
authors.initials: L
authors.lastname: Liotta
authors.forename: Emanuel
authors.initials: E
authors.lastname: Petricoin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D047569:Laser Scanning Cytometry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors