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Identification of putative serum glycoprotein biomarkers for human lung adenocarcinoma by multilectin affinity chromatography and LC-MSMS.

Cited 116 time in Web of Science Cited 126 time in Scopus
Authors
Ryoo, Hyun-Mo; Heo, Sun-Hee; Lee, Seung-Jin; Park, Jae-Yong; Cho, Je-Yoel
Issue Date
2007-10
Publisher
Wiley-Blackwell
Citation
Proteomics 2007, 7, 4292-4302
Keywords
BiomarkersGlycoproteomeHuman serumLung adenocarcinomaMultilectin affinity column
Abstract
Glycoproteins in human serum play fundamental roles in many biological processes, and also have clinical value as biomarkers for disease progression and treatment. In this study, we isolated glycoproteins from the sera of three healthy individuals and three lung adenocarcinoma patients using multilectin affinity chromatography. The recovered glycoproteins were subjected to treatment with peptide-N-glycosidase F (PNGase F) and in-gel digestion by trypsin. Tryptic peptides were analyzed by nano-LC coupled to ESI-MS/MS and the MS/MS spectra were processed by Bioworks 3.2 and an in-house bioinformatics tool, ProtAn. Approximately 90% of the proteins identified contained more than one potential glycosylation site. Comparison of the serum glycoproteome of healthy and adenocarcinoma individuals revealed 38 cancer-selective proteins. Among them, 60% have previously been reported as low abundance proteins in human sera. We identified several cancer-selective proteins that have been previously characterized as potential indicators of lung cancer in serum or plasma, including haptoglobin (HP), inter--trypsin inhibitor heavy chain 4 (ITI-H4), complement C3 precursor, and leucine-rich -2-glycoprotein. In addition, plasma kallikrein (KLKB1) and inter--trypsin inhibitor heavy chain 3 (ITI-H3) were identified as being potentially elevated in the lung cancer group, and were validated by Western blot analysis. Furthermore, 18 kDa plasma kallirein protein fragment was detected at high levels in 25 out of 28 adenocarcinoma patients, while one of the eight normal individuals showed moderate positive. The results suggest that KLKB1 represents a potential candidate serum biomarker of lung cancer.
ISSN
1615-9853
Language
English
URI
http://hdl.handle.net/10371/69739
DOI
https://doi.org/10.1002/pmic.200700433
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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