title: Glycoproteomic analysis of serum from patients with gastric precancerous lesions.
abstract: Gastric cancer is preceded by a carcinogenesis pathway that includes gastritis caused by Helicobacter pylori infection, chronic atrophic gastritis that may progress to intestinal metaplasia (IM), dysplasia, and ultimately gastric carcinoma of the more common intestinal subtype. The identification of glycosylation changes in circulating serum proteins in patients with precursor lesions of gastric cancer is of high interest and represents a source of putative new biomarkers for early diagnosis and intervention. This study applies a glycoproteomic approach to identify altered glycoproteins expressing the simple mucin-type carbohydrate antigens T and STn in the serum of patients with gastritis, IM (complete and incomplete subtypes), and control healthy individuals. The immunohistochemistry analysis of the gastric mucosa of these patients showed expression of T and STn antigens in gastric lesions, with STn being expressed only in IM. The serum glycoproteomic analysis using 2D-gel electrophoresis, Western blot, and MALDI-TOF/TOF mass spectrometry led to the identification of circulating proteins carrying these altered glycans. One of the glycoproteins identified was plasminogen, a protein that has been reported to play a role in H. pylori chronic infection of the gastric mucosa and is involved in extracellular matrix modeling and degradation. Plasminogen was further characterized and showed to carry STn antigens in patients with gastritis and IM. These results provide evidence of serum proteins displaying abnormal O-glycosylation in patients with precursor lesions of gastric carcinoma and include a panel of putative targets for the non-invasive clinical diagnosis of individuals with gastritis and IM.
authors: Institute of Molecular Pathology and Immunology University of Porto, IPATIMUP, Porto, Portugal.
authors: Catarina
authors: C
authors: Gomes
authors: Andreia
authors: A
authors: Almeida
authors: José Alexandre
authors: JA
authors: Ferreira
authors: Luísa
authors: L
authors: Silva
authors: Hugo
authors: H
authors: Santos-Sousa
authors: João
authors: J
authors: Pinto-de-Sousa
authors: Lúcio L
authors: LL
authors: Santos
authors: Francisco
authors: F
authors: Amado
authors: Tilo
authors: T
authors: Schwientek
authors: Steven B
authors: SB
authors: Levery
authors: Ulla
authors: U
authors: Mandel
authors: Henrik
authors: H
authors: Clausen
authors: Leonor
authors: L
authors: David
authors: Celso A
authors: CA
authors: Reis
authors: Hugo
authors: H
authors: Osório
mesh_terms: D015153:Blotting, Western; D002241:Carbohydrates / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D011230:Precancerous Conditions / Q000097:blood*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000097:blood*
chemical_list: D002241:Carbohydrates