Probing the O-Glycoproteome of Gastric Cancer Cell Lines for Biomarker Discovery

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

Campos, D (Autor) Outra; Freitas, D (Autor) Outra; Gomes, J (Autor) Outra; Magalhaes, A (Autor) Outra; Steentoft, C (Autor) Outra; Gomes, C (Autor) Outra; Vester Christensen, MB (Autor) Outra; Ferreira, JA (Autor) Outra; Afonso, LP (Autor) Outra; Santos, LL (Autor) Outra; de Sousa, JP (Autor) Outra; Mandel, U (Autor) Outra; Clausen, H (Autor) Outra; Vakhrushev, SY (Autor) Outra; Celso Reis (Autor) ICBAS

Revista

Título: MOLECULAR & CELLULAR PROTEOMICS

Vol. 14

Páginas: 1616-1629

ISSN: 1535-9476

Editora: Elsevier

Indexação

ISI Web of Knowledge - 68 Citações

Scopus - 70 Citações

Outras Informações

ID Authenticus: P-00G-5Z3

DOI: 10.1074/mcp.m114.046862

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14