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Lookup NU author(s): Dr Joseph Gray, Dr Dipanker Chattopadhyay, Dr Gary Beale, Dr Gillian Patman, Dr Luca Miele, Dr Barry King, Dr Stephen Stewart, Dr Mark Hudson, Professor Chris Day, Professor Derek Manas, Professor Helen ReevesORCiD
Background: Non-alcoholic fatty liver disease (NAFLD) has a prevalence of over 20% in Western societies. Affected individuals are at risk of developing both cirrhosis and hepatocellular cancer (HCC). Presently there is no cost effective population based means of identifying cirrhotic individuals and even if there were, our ability to perform HCC surveillance in the at risk group is inadequate. We have performed a pilot proteomic study to assess this as a strategy for serum biomarker detection. Methods: 2D Gel electrophoresis was performed on immune depleted sera from 3 groups of patients, namely those with (1) pre-cirrhotic NAFLD (2) cirrhotic NAFLD and (3) cirrhotic NAFLD with co-existing HCC. Five spots differentiating at least one of these three groups were characterised by mass spectroscopy. An ELISA assay was optimised and a cross sectional study assessing one of these serum spots was performed on serum from 45 patients with steatohepatitis related cirrhosis and HCC and compared to 77 patients with histologically staged steatohepatitis. Results: Four of the spots identified were apolipoprotein isoforms, the pattern of which was able to differentiate the three groups. The 5th spot, seen in the serum of cirrhotic individuals and more markedly in those with HCC, was identified as CD5 antigen like (CD5L). By ELISA assay, although CD5L was markedly elevated in a number of cirrhotic individuals with HCC, its overall ability to distinguish non-cancer from cancer individuals as determined by AUC ROC analysis was poor. However, serum CD5L was dramatically increased, independently of age, sex, and the presence of necroinflammation, in the serum of individuals with NAFLD cirrhosis relative to those with pre-cirrhotic disease. Conclusion: This novel proteomic strategy has identified a number of candidate biomarkers which may have benefit in the surveillance and diagnosis of individuals with chronic liver disease and/or HCC.
Author(s): Gray J, Chattopadhyay D, Beale GS, Patman GL, Miele L, King BP, Stewart S, Hudson M, Day CP, Manas DM, Reeves HL
Publication type: Article
Publication status: Published
Journal: BMC Cancer
Year: 2009
Volume: 9
Date deposited: 17/02/2010
ISSN (print): 1471-2407
ISSN (electronic):
Publisher: BioMed Central Ltd.
URL: http://dx.doi.org/10.1186/1471-2407-9-271
DOI: 10.1186/1471-2407-9-271
Notes: Article number 271
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