TY - JOUR
T1 - Glycomic alterations in the highly-abundant and lesser-abundant blood serum protein fractions for patients diagnosed with hepatocellular carcinoma
AU - Kang, Pilsoo
AU - Madera, Milan
AU - Alley, William R.
AU - Goldman, Radoslav
AU - Mechref, Yehia
AU - Novotny, Milos V.
N1 - Funding Information:
This work was supported by Grant No. UO1 CA128535-03 from the National Cancer Institute , a component of the National Institutes of Health to M.V.N. and Grant No. RR018942 from the National Center for Research Resources , a component of the National Institutes of Health (NIH-NCRR) for the National Center of Glycomics and Glycoproteomics (NCGG) at Indiana University, directed by M.V.N. Additionally, support to R.G. from Grant No. R01CA115625 and R01CA135069, National Cancer Institute is gratefully acknowledged.
PY - 2011/8/15
Y1 - 2011/8/15
N2 - Hepatocellular cancer (HCC) is a serious human disease with an unfortunately low survival rate. It further poses a significant epidemic threat to our society through its viral vectors associated with cirrhosis conditions preceding the cancer. A search for biomarkers of these diseases enlists analytical glycobiology, in general, and quantitative biomolecular mass spectrometry (MS), in particular, as valuable approaches to cancer research. The recent advances in quantitative glycan permethylation prior to MALDI-MS oligosaccharide profiling has enabled us to compare the glycan quantitative proportions in the small serum samples of cancer and cirrhotic patients against control individuals. In this investigation, reasoning that some of the observed glycomic changes could be at least partly explained by acute-phase or immune responses, we further fractionated the major serum proteins from the minor components and compared statistically their differential glycosylation, elucidating some causes of quantitatively unusual glycosylation events. Numerous glycan structures were identified and tentatively connected with their originating proteins, with a particular emphasis on sialylated and fucosylated glycans. In particular, for the highly-abundant protein fraction, several smaller, neutral glycans were observed to be different between disease-free individuals and those diagnosed with either HCC or cirrhosis. Further, these types of glycans were also different between the two diseases. In the lesser-abundant protein fraction, a number of sialylated glycans were different between each state-of-health.
AB - Hepatocellular cancer (HCC) is a serious human disease with an unfortunately low survival rate. It further poses a significant epidemic threat to our society through its viral vectors associated with cirrhosis conditions preceding the cancer. A search for biomarkers of these diseases enlists analytical glycobiology, in general, and quantitative biomolecular mass spectrometry (MS), in particular, as valuable approaches to cancer research. The recent advances in quantitative glycan permethylation prior to MALDI-MS oligosaccharide profiling has enabled us to compare the glycan quantitative proportions in the small serum samples of cancer and cirrhotic patients against control individuals. In this investigation, reasoning that some of the observed glycomic changes could be at least partly explained by acute-phase or immune responses, we further fractionated the major serum proteins from the minor components and compared statistically their differential glycosylation, elucidating some causes of quantitatively unusual glycosylation events. Numerous glycan structures were identified and tentatively connected with their originating proteins, with a particular emphasis on sialylated and fucosylated glycans. In particular, for the highly-abundant protein fraction, several smaller, neutral glycans were observed to be different between disease-free individuals and those diagnosed with either HCC or cirrhosis. Further, these types of glycans were also different between the two diseases. In the lesser-abundant protein fraction, a number of sialylated glycans were different between each state-of-health.
KW - Glycans
KW - Glycomics
KW - Hepatocellular carcinoma
KW - Immunoaffinity fractionation
KW - MALDI-TOF MS
KW - Permethylation
UR - http://www.scopus.com/inward/record.url?scp=80051548612&partnerID=8YFLogxK
U2 - 10.1016/j.ijms.2010.11.007
DO - 10.1016/j.ijms.2010.11.007
M3 - Article
AN - SCOPUS:80051548612
SN - 1387-3806
VL - 305
SP - 185
EP - 198
JO - International Journal of Mass Spectrometry
JF - International Journal of Mass Spectrometry
IS - 2-3
ER -