J Liver Cancer.  2018 Mar;18(1):33-43. 10.17998/jlc.18.1.33.

Methionine Adenosyltransferase 1: A Proteomic Surrogate Marker of Early Hepatocellular Carcinoma in Cirrhotic Patients

Affiliations
  • 1Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
  • 2Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. s5854@amc.seoul.kr
  • 3Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 4Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 5Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

BACKGROUND/AIMS
Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers.
METHODS
We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC.
RESULTS
Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients.
CONCLUSIONS
MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.

Keyword

Hepatocellular carcinoma; Liver cirrhosis; Proteomics; Western blot; Methionine adenosyltransferase
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