Differential N-glycosylation patterns in lung adenocarcinoma tissue

L. Renee Ruhaak, Sandra L. Taylor, Carol Stroble, Uyen Thao Nguyen, Evan A. Parker, Ting Song, Carlito B Lebrilla, William N. Rom, Harvey Pass, Kyoungmi Kim, Karen Kelly, Suzanne Miyamoto

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

To decrease the mortality of lung cancer, better screening and diagnostic tools as well as treatment options are needed. Protein glycosylation is one of the major post-translational modifications that is altered in cancer, but it is not exactly clear which glycan structures are affected. A better understanding of the glycan structures that are differentially regulated in lung tumor tissue is highly desirable and will allow us to gain greater insight into the underlying biological mechanisms of aberrant glycosylation in lung cancer. Here, we assess differential glycosylation patterns of lung tumor tissue and nonmalignant tissue at the level of individual glycan structures using nLC-chip-TOF-MS. Using tissue samples from 42 lung adenocarcinoma patients, 29 differentially expressed (FDR <0.05) glycan structures were identified. The levels of several oligomannose type glycans were upregulated in tumor tissue. Furthermore, levels of fully galactosylated glycans, some of which were of the hybrid type and mostly without fucose, were decreased in cancerous tissue, whereas levels of non- or low-galactosylated glycans mostly with fucose were increased. To further assess the regulation of the altered glycosylation, the glycomics data was compared to publicly available gene expression data from lung adenocarcinoma tissue compared to nonmalignant lung tissue. The results are consistent with the possibility that the observed N-glycan changes have their origin in differentially expressed glycosyltransferases. These results will be used as a starting point for the further development of clinical glycan applications in the fields of imaging, drug targeting, and biomarkers for lung cancer.

Original languageEnglish (US)
Pages (from-to)4538-4549
Number of pages12
JournalJournal of Proteome Research
Volume14
Issue number11
DOIs
StatePublished - Nov 6 2015

Keywords

  • gene expression
  • N-Glycosylation
  • nLC-MS profiling
  • NSCLC
  • tissue

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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  • Cite this

    Ruhaak, L. R., Taylor, S. L., Stroble, C., Nguyen, U. T., Parker, E. A., Song, T., Lebrilla, C. B., Rom, W. N., Pass, H., Kim, K., Kelly, K., & Miyamoto, S. (2015). Differential N-glycosylation patterns in lung adenocarcinoma tissue. Journal of Proteome Research, 14(11), 4538-4549. https://doi.org/10.1021/acs.jproteome.5b00255