PepCon-2015
Nanjing·China
Title: Discovery of Glycoproteins as a Cancer Biomarker in Human Plasma by
Mass Spectrometry
Dr. Jong Shin Yoo* and Xinyuan Liu
Director, Mass Spectrometry Division, Korea Basic Science Institute, Republic of Korea
Abstract
Due to the dynamic reflection of organ functions of human plasma in health and disease and feasible link to clinical data, it is
normally required to detect secreted proteins from plasma in order to discover the useful cancer biomarkers. Plasma has a wide range
of protein complexity, very large number of proteins from most protein components in the body with extensive posttranslational
modifications and physiological and temporal variations. We need to analyze large number of samples and controls of plasma with
wide dynamic range. To discover candidate disease markers in the human plasma, therefore, is challenging in proteomics.
We used pooled plasma sample of normal and cancer patients to statistically profile the peptide patterns from the plasma proteins by
mass spectrometry (MS). From the peptide pattern profiling with label-free quantitative MS analysis, we selected a group of peptides
from glycoproteins, each of which showed quite different quantity from other peptides belonging to the same glycoproteins. We
verified that the steric effect of N-linked glycan in a protein can make the protein not cleaved well by trypsin. Most of the selected
peptides were next to the N-linked glycosylation sites and the amount was decreased in liver cancer case. Those N-linked
glycosylation sites in a protein were confirmed by the comparison of deglycosylated peptides with nonglycosylated peptides in same
peptide sequence. The panel peptides digested from highly abundant proteins in plasma was further validated by a single LC/MS
using multiple reaction monitoring technique for a biomarker discovery.
Biography
Dr Yoo completed his doctorate in analytical chemistry with the theoretical and practical combination of mass spectrometry and
liquid chromatography at the Michigan State University in 1992. After his analytical study of glycans with mass spectrometry in
Harvard School of Public Health as a post doctorate, he joined the Mass Spectrometry Division at Korea Basic Science Institute in
1993, where he directed his research to high throughput proteomics with mass spectrometry. This led to the development of
multidimensional analysis of proteome in human plasma in 2004 and human brain in 2006 with connection to HUPO initiatives. Dr.
Yoo served his presidency of Korean Society of Mass Spectrometry in 2006-2007. He is also joining the presidency of Korean
HUPO from 2008. Dr.Yoo pioneered a new technology for the high throughput analysis of human proteomes and identification of
their post translational modification such as acetylation in 2001 and phosphorylation in 2007. This technology is capable of label free
quantitation of the proteins in normal plasma as well as cancer case. It is expected that this work will lead to the development of
novel biomakers linked to highly abundant proteins in human plasma. Concurrently, Dr. Yoo is applying ultra-high resolution mass
spectrometry technology with 15T FTICR for the analysis of glycoproteins in human plasma for the biomarker discovery and
validation. He is also joining the presidency of Korean HUPO from 2008.