Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

被引:41
作者
Dive, C. [3 ]
Smith, R. A. [2 ]
Garner, E. [2 ]
Ward, T. [3 ]
St George-Smith, S. [3 ]
Campbell, F. [4 ]
Greenhalf, W. [2 ]
Ghaneh, P. [2 ]
Neoptolemos, J. P. [1 ,2 ]
机构
[1] Royal Liverpool Univ Hosp, Owen & Ellen Evans Chair Canc Studies, Liverpool Canc Res UK Ctr, NIHR Pancreas Biomed Res Unit, Liverpool L69 3GA, Merseyside, England
[2] Royal Liverpool Univ Hosp, Liverpool Expt Canc Med Ctr, Liverpool L69 3GA, Merseyside, England
[3] Univ Manchester, Clin & Expt Pharmacol Grp, Paterson Inst Canc Res, Manchester, Lancs, England
[4] Royal Liverpool Univ Hosp, Dept Pathol, Liverpool L7 8XP, Merseyside, England
关键词
pancreatic cancer; cytokeratin; 18; circulating biomarker; M65; M30; necrosis; apoptosis; CASPASE-CLEAVED CYTOKERATIN-18; ELEVATED SERUM-LEVELS; CELL-DEATH; LUNG-CANCER; CIRCULATING BIOMARKERS; APOPTOSIS; M30; TUMOR; M65; VALIDATION;
D O I
10.1038/sj.bjc.6605494
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer. METHODS: Plasma samples from 103 patients with pancreatic cancer stored at -80 degrees C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23-57) months. Patients with metastatic disease (n = 19) were found to have greater median (IQR) M65 levels (1145 (739-1698) Ul(-1)) compared with the locally advanced (n = 20; 748 (406-1150) Ul(-1)) and resected (n = 64; 612 (331-987) Ul(-1)) patients (P = 0.002). Elevated M65 levels were associated with poorer overall survival on univariate (P<0.001) but not multivariate (P = 0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum-bilirubin levels (P<0.001) and the duration of plasma storage (P<0.001). CONCLUSIONS: Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors. British Journal of Cancer (2010) 102, 577-582. doi:10.1038/sj.bjc.6605494 www.bjcancer.com Published online 5 January 2010 (C) 2010 Cancer Research UK
引用
收藏
页码:577 / 582
页数:6
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