A1 Refereed original research article in a scientific journal

N-glycomic Profiling as a Tool to Separate Rectal Adenomas from Carcinomas




AuthorsKaprio T, Satomaa T, Heiskanen A, Hokke CH, Deelder AM, Mustonen H, Hagström J, Carpen O, Saarinen J, Haglund C

PublisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Publication year2015

JournalMolecular and Cellular Proteomics

Journal name in sourceMOLECULAR & CELLULAR PROTEOMICS

Journal acronymMOL CELL PROTEOMICS

Volume14

Issue2

First page 277

Last page288

Number of pages12

ISSN1535-9476

DOIhttps://doi.org/10.1074/mcp.M114.041632


Abstract
All human cells are covered by glycans, the carbohydrate units of glycoproteins, glycolipids, and proteoglycans. Most glycans are localized to cell surfaces and participate in events essential for cell viability and function. Glycosylation evolves during carcinogenesis, and therefore carcinoma-related glycan structures are potential cancer biomarkers. Colorectal cancer is one of the world's three most common cancers, and its incidence is rising. Novel biomarkers are essential to identify patients for targeted and individualized therapy. We compared the N-glycan profiles of five rectal adenomas and 18 rectal carcinomas of different stages by matrix-assisted laser desorptionionization time-of-flight mass spectrometry. Paraffin-embedded tumor samples were deparaffinized, and glycans were enzymatically released and purified. We found differences in glycosylation between adenomas and carcinomas: monoantennary, sialylated, pauci-mannose, and small high-mannose N-glycan structures were more common in carcinomas than in adenomas. We also found differences between stage I-II and stage III carcinomas. Based on these findings, we selected two glycan structures: pauci-mannose and sialyl Lewis a, for immunohistochemical analysis of their tissue expression in 220 colorectal cancer patients. In colorectal cancer, poor prognosis correlated with elevated expression of sialyl Lewis a, and in advanced colorectal cancer, poor prognosis correlated with elevated expression of pauci-mannose. In conclusion, by mass spectrometry we found several carcinoma related glycans, and we demonstrate a method of transforming these results into immunohistochemistry, a readily applicable method to study biomarker expression in patient samples.



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