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Author(s): Campos, D
Freitas, D
Gomes, J
Magalhães, A
Steentoft, C
Gomes, C
Vester-Christensen, M
Ferreira, JA
Afonso, L
Santos, L
Sousa, J
Mandel, U
Clausen, H
Vakhrushev, S
Reis, CA
Title: Probing the O-glycoproteome of gastric cancer cell lines for biomarker discovery
Publisher: American Society for Biochemistry and Molecular Biology
Issue Date: 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 "Simple- Cell" (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.
Subject: Aged
Aged, 80 and over
Biomarkers, Tumor/blood
Biomarkers, Tumor/metabolism
Cell Line, Tumor
Middle Aged
Stomach Neoplasms/blood
Stomach Neoplasms/metabolism
Source: Molecular and Cellular Proteomics, vol.14(6), p. 1616-1629
Related Information: info:eu-repo/grantAgreement/FCT/COMPETE/125428/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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