Enrichment strategies in glycomics-based lung cancer biomarker development

L. Renee Ruhaak, Uyen Thao Nguyen, Carol Stroble, Sandra L. Taylor, Ayumu Taguchi, Samir M. Hanash, Carlito B Lebrilla, Kyoungmi Kim, Suzanne Miyamoto

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Purpose: There is a need to identify better glycan biomarkers for diagnosis, early detection, and treatment monitoring in lung cancer using biofluids such as blood. Biofluids are complex mixtures of proteins dominated by a few high abundance proteins that may not have specificity for lung cancer. Therefore, two methods for protein enrichment were evaluated; affinity capturing of IgG and enrichment of medium abundance proteins, thus allowing us to determine which method yields the best candidate glycan biomarkers for lung cancer. Experimental design: N-glycans isolated from plasma samples from 20 cases of lung adenocarcinoma and 20 matched controls were analyzed using nLC-PGC-chip-TOF-MS (where PGC is porous-graphitized carbon). N-glycan profiles were obtained for five different fractions: total plasma, isolated IgG, IgG-depleted plasma, and the bound and flow-through fractions of protein enrichment. Results: Four glycans differed significantly (false discovery rate, FDR < 0.05) between cases and controls in whole unfractionated plasma, while four other glycans differed significantly by cancer status in the IgG fraction. No significant glycan differences were observed in the other fractions. Conclusions and clinical relevance: These results confirm that the N-glycan profile in plasma of lung cancer patients is different from healthy controls and appears to be dominated by alterations in relatively abundant proteins.

Original languageEnglish (US)
Pages (from-to)664-676
Number of pages13
JournalProteomics - Clinical Applications
Volume7
Issue number9-10
DOIs
StatePublished - 2013

Keywords

  • Biomarker
  • Mass spectrometry
  • N-glycan
  • Nonsmall cell lung cancer
  • Protein enrichment

ASJC Scopus subject areas

  • Clinical Biochemistry

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  • Cite this

    Ruhaak, L. R., Nguyen, U. T., Stroble, C., Taylor, S. L., Taguchi, A., Hanash, S. M., Lebrilla, C. B., Kim, K., & Miyamoto, S. (2013). Enrichment strategies in glycomics-based lung cancer biomarker development. Proteomics - Clinical Applications, 7(9-10), 664-676. https://doi.org/10.1002/prca.201200131