A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease.
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.


CONCLUSIONS
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.
Gray
Joe
J
Northern Institute for Cancer Research, The Medical School, Newcastle University, Newcastle-upon-Tyne, UK. joe.gray@ncl.ac.uk
Chattopadhyay
Dipankar
D
Beale
Gary S
GS
Patman
Gillian L
GL
Miele
Luca
L
King
Barry P
BP
Stewart
Stephen
S
Hudson
Mark
M
Day
Christopher P
CP
Manas
Derek M
DM
Reeves
Helen L
HL
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000097:blood*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms; D040901:Proteomics / Q000379:methods*; D012306:Risk
D014408:Biomarkers, Tumor; D020033:Protein Isoforms