Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans.
Chronic infection with hepatitis B virus (HBV) is associated with the majority of hepatocellular carcinoma (HCC). The diagnosis of HCC is usually made in the late stages of the disease, when treatment options are limited and prognosis is poor. We therefore have developed a method of glycoproteomic analysis in an attempt to discover serum markers that can assist in the early detection of HBV-induced liver cancer. Briefly, a comparative method for analysis of oligosaccharides released from serum glycoproteins and for recovery and identification of proteins with aberrant glycosylation, as a function of cancer diagnosis, is described. The model we have used is the woodchuck (Marmota monax), which shares similarities in the glycosylation pattern associated with liver proteins in human HCC. In this report, we show that woodchucks diagnosed with HCC have dramatically higher levels of serum-associated core alpha-1,6-linked fucose, as compared with woodchucks without a diagnosis of HCC. The coupling of this methodology with 2D gel proteomics has permitted the identification of several glycoproteins with altered glycosylation as a function of cancer. One such glycoprotein, Golgi Protein 73 (GP73), was found to be elevated and hyperfucosylated in animals with HCC. Further, the study showed GP73 to be elevated in the serum of people with a diagnosis of HCC, providing a validation of our approach. The potential of this technology for biomarker discovery and the implications of increased levels of GP73 in liver cancer are discussed.
Block
Timothy M
TM
Drexel Institute for Biotechnology and Virology Research, Drexel University, Doylestown, PA 18901, USA. tim.block@drexel.edu
Comunale
Mary Ann
MA
Lowman
Melissa
M
Steel
Laura F
LF
Romano
Patrick R
PR
Fimmel
Claus
C
Tennant
Bud C
BC
London
W Thomas
WT
Evans
Alison A
AA
Blumberg
Baruch S
BS
Dwek
Raymond A
RA
Mattu
Tajinder S
TS
Mehta
Anand S
AS
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D015180:Electrophoresis, Gel, Two-Dimensional; D005643:Fucose / Q000032:analysis; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D008392:Marmota; D008565:Membrane Proteins / Q000097:blood / Q000737:chemistry; D009844:Oligosaccharides / Q000032:analysis; D040901:Proteomics / Q000379:methods*
D014408:Biomarkers, Tumor; C410824:GOLM1 protein, human; D006023:Glycoproteins; D008565:Membrane Proteins; D009844:Oligosaccharides; D005643:Fucose