Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer

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Hua S., Williams C. C., Dimapasoc L. M., Ro G. S., Ozcan S., Miyamoto S., ...More

JOURNAL OF CHROMATOGRAPHY A, vol.1279, pp.58-67, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 1279
  • Publication Date: 2013
  • Doi Number: 10.1016/j.chroma.2012.12.079
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.58-67
  • Keywords: Chip nano-LC/MS, Cancer biomarker, Glycan isomer separation, Rapid-throughput, Structure-specific profiling, Serum glycan, MASS-SPECTROMETRY, LIQUID-CHROMATOGRAPHY, PROSTATE-CANCER, LINKED GLYCANS, CELL-LINES, SERUM, GLYCOSYLATION, DISCOVERY, GLYCOPROTEINS, OLIGOSACCHARIDES
  • Middle East Technical University Affiliated: Yes


Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry. To demonstrate the utility of this method, we analyzed and compared serum samples from epithelial ovarian cancer cases (n = 46) and healthy control individuals (n = 48). Over 250 N-linked glycan compound peaks with over 100 distinct N-linked glycan compositions were identified. Statistical testing identified 26 potential glycan biomarkers based on both compositional and structure-specific analyses. Using these results, an optimized model was created incorporating the combined abundances of seven potential glycan biomarkers. The receiver operating characteristic (ROC) curve of this optimized model had an area under the curve (AUC) of 0.96, indicating robust discrimination between cancer cases and healthy controls. Rapid-throughput chromatographic glycan profiling was found to be an effective platform for structure-specific biomarker discovery. (C) 2013 Elsevier B.V. All rights reserved.