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Probing the O-glycoproteome of gastric cancer cell lines for biomarker discovery.
- Source :
-
Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2015 Jun; Vol. 14 (6), pp. 1616-29. Date of Electronic Publication: 2015 Mar 26. - Publication Year :
- 2015
-
Abstract
- Circulating O-glycoproteins shed from cancer cells represent important serum biomarkers for diagnostic and prognostic purposes. We have recently shown that selective detection of cancer-associated aberrant glycoforms of circulating O-glycoprotein biomarkers can increase specificity of cancer biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO "SimpleCell" (SC) strategy to characterize the O-glycoproteome of two gastric cancer SimpleCell lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses at least partially truncated O-glycans. Overall, we identified 499 O-glycoproteins and 1236 O-glycosites in gastric cancer SimpleCells, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer and healthy individuals to identify circulating O-glycoproteins with the STn glycoform. We identified 37 O-glycoproteins in the pool of cancer sera, and only nine of these were also found in sera from healthy individuals. Two identified candidate O-glycoprotein biomarkers (CD44 and GalNAc-T5) circulating with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to show that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set of O-glycoprotein candidates with biomarker potential in gastric cancer.<br /> (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Aged
Aged, 80 and over
Biomarkers, Tumor blood
Cell Line, Tumor
Female
Glycoproteins blood
Humans
Male
Middle Aged
N-Acetylgalactosaminyltransferases blood
Proteome
Stomach Neoplasms blood
Polypeptide N-acetylgalactosaminyltransferase
Biomarkers, Tumor metabolism
Glycoproteins metabolism
N-Acetylgalactosaminyltransferases metabolism
Stomach Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1535-9484
- Volume :
- 14
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular & cellular proteomics : MCP
- Publication Type :
- Academic Journal
- Accession number :
- 25813380
- Full Text :
- https://doi.org/10.1074/mcp.M114.046862