Evaluation in pre-diagnosis samples discounts ICAM-1 and TIMP-1 as biomarkers for earlier diagnosis of pancreatic cancer

被引:35
作者
Jenkinson, C. [1 ,2 ]
Elliott, V. [1 ]
Menon, U. [3 ]
Apostolidou, S. [3 ]
Fourkala, O. E. [3 ]
Gentry-Maharaj, A. [3 ]
Pereira, S. P. [4 ,5 ,6 ]
Jacobs, I. [3 ,5 ,6 ]
Cox, T. F. [1 ]
Greenhalf, W. [1 ]
Timms, J. F. [3 ]
Sutton, R. [1 ,2 ]
Neoptolemos, J. P. [1 ,2 ]
Costello, E. [1 ,2 ]
机构
[1] Univ Liverpool, NIHR Liverpool Pancreas Biomed Res Unit, Liverpool L69 3GA, Merseyside, England
[2] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool L69 3GA, Merseyside, England
[3] UCL, Inst Womens Hlth, London WC1E 6BT, England
[4] UCL, Inst Liver & Digest Hlth, London NW3 2QG, England
[5] NHS Fdn Trust, Univ Coll Hosp, Dept Gastroenterol, London NW1 2BU, England
[6] Univ Manchester, Core Technol Facil 1 018, Fac Med & Human Sci, Manchester M13 9NT, Lancs, England
基金
英国医学研究理事会;
关键词
ICAM-1; TIMP-1; Pancreatic cancer; Serum biomarker; UKCTOCS; TISSUE INHIBITOR; PLASMA;
D O I
10.1016/j.jprot.2014.10.001
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Circulating intercellular adhesion molecule-1 (ICAM-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been widely proposed as potential diagnostic biomarkers for pancreatic ductal adenocarcinoma (PDAC). We report on serum protein levels prior to clinical presentation of pancreatic cancer. Serum ICAM-1 and TIMP-1 were measured by ELISA in two case-control sets: 1) samples from patients diagnosed with pancreatic cancer (n = 40), chronic pancreatitis (n = 20), benign jaundice due to gall stones (n = 20) and healthy subjects (n = 20); 2) a preclinical set from the UK Collaborative Trial of Ovarian Cancer Screening biobank of samples collected from 27 post-menopausal women 0-12 months prior to diagnosis of pancreatic cancer and controls matched for date of donation and centre. Levels of ICA1vI-1 and TIMP-1 were significantly elevated in set 1 in PDAC patients with jaundice compared to PDAC patients without jaundice and both proteins were elevated in patients with jaundice due to gall stones. Neither protein was elevated in samples taken 0-12 months prior to PDAC diagnosis compared to non-cancer control samples. In conclusion, evaluation in pre-diagnosis samples discounts ICAM-1 and TIMP-1 as biomarkers for earlier diagnosis of pancreatic cancer. Failure to account for obstructive jaundice may have contributed to the previous promise of these candidate biomarkers. Biological significance Pancreatic cancer is usually diagnosed when at an advanced stage which greatly limits therapeutic options. Biomarkers that could facilitate earlier diagnosis are urgently sought. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:400 / 402
页数:3
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