Molecular Diagnostics
British Journal of Cancer (2009) 100, 1659–1665. doi:10.1038/sj.bjc.6605033 www.bjcancer.com
Published online 14 April 2009
The use of kallikrein-related peptidases as adjuvant prognostic markers in colorectal cancer
M Talieri1, L Li2, Y Zheng2, D K Alexopoulou1, A Soosaipillai3, A Scorilas4, D Xynopoulos5 and E P Diamandis3
- 1Department of Cellular Physiology, 'G. Papanicolaou' Research Center of Oncology, 'Saint Savvas' Hospital, 171 Alexandras Avenue, Athens 11522, Greece
- 2Department of Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, North Seattle WA 98109-1024, USA
- 3Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto, 60 Murray Street, 6th Floor, Room L6-2001, Toronto, ON, Canada M5T 3L9
- 4Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimioupolis, Athens 15701, Greece
- 5Department of Gastroenterology, 'Saint Savvas' Hospital, 171 Alexandras Avenue, Athens 11522, Greece
Correspondence: Dr M Talieri, E-mail: talieri@agsavvas-hosp.gr
Received 19 December 2008; Revised 18 March 2009; Accepted 19 March 2009; Published online 14 April 2009.
Abstract
Several members of the human tissue kallikrein-related peptidase (KLK) family are emerging cancer biomarkers. The aim of this study was to analyse the expression of a panel of KLKs in colorectal cancer and to find out if the multiparametric combination of them can increase the accuracy of prediction of patients survival beyond the traditional clinical information. Nine KLKs (KLK5-8, KLK10, KLK11, KLK13-15) were measured using ELISA assays in cytosolic extracts of 122 colon cancer tissues and their nearby normal mucosa, obtained during surgery. The mean levels of almost all KLKs in tumour tissues were significantly different from their counterparts of normal tissue (P<0.0001). KLK 5, 6, 7, 13, 14 were significantly associated with overall survival in univariate analysis, but after adjusting for age, TNM and differentiation stage, only KLK5 (HR: 1.24 (95% CI: 1.05–1.47)), KLK7 (HR: 1.57 (95% CI: 1.04–2.37)) and KLK14 (HR: 1.43 (95% CI: 1.05–1.94)) remained significant. Addition of a panel of selected KLK markers to clinical parameters gave an increment in AUC of 0.86 beyond the clinical factors at year 1, showing that it can increase the accuracy of prediction of overall survival beyond the traditional clinical information, particularly the short-term (1 year) survival after surgery.
Keywords:
colorectal cancer, ELISA, kallikrein-related peptidases, KLKs, tumour markers
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