Probing the O-glycoproteome of Gastric Cancer Cell Lines for Biomarker Discovery (original) (raw)
2015, Molecular & Cellular Proteomics
Circulating O-glycoproteins shed from cancer cells represent important serum biomarkers for diagnostic and prognostic purposes. We have recently shown that selective detection of cancerassociated aberrant glycoforms of circulating O-glycoprotein biomarkers can increase specificity of cancer biomarker assays. However, the current knowledge of secreted and circulating Oglycoproteins is limited. Here, we used the "SimpleCell" (SC) strategy to characterize the Oglycoproteome of two gastric cancer SC lines (AGS, MKN45) and as well as a wild type cell line (KATO III) naturally expressing truncated O-glycosylation. Overall we identified 499 Oglycoproteins and 1,236 O-glycosites in gastric cancer SCs, and a total 47 O-glycoproteins and 73 Oglycosites 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 9 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 demonstrate 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. Version: Postprint (identical content as published paper) This is a self-archived document from i3S-Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/
Loading Preview
Sorry, preview is currently unavailable. You can download the paper by clicking the button above.