Comprehensive quantitative analysis of ovarian and breast cancer tumor peptidomes

Zhe Xu, Chaochao Wu, Fang Xie, Gordon W. Slysz, Nikola Tolic, Matthew E. Monroe, Vladislav A. Petyuk, Samuel H. Payne, Grant M. Fujimoto, Ronald J. Moore, Thomas L. Fillmore, Athena A. Schepmoes, Douglas A. Levine, R. Reid Townsend, Sherri R. Davies, Shunqiang Li, Matthew Ellis, Emily Boja, Robert Rivers, Henry RodriguezKarin D. Rodland, Tao Liu, Richard D. Smith

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high-throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with postexcision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics and provides insights not readily obtainable from such approaches.

Original languageEnglish
Pages (from-to)422-433
Number of pages12
JournalJournal of Proteome Research
Volume14
Issue number1
DOIs
StatePublished - Jan 2 2015

Keywords

  • breast cancer
  • ischemia
  • ovarian cancer
  • peptidomics
  • proteases
  • protein degradation
  • tumor

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    Xu, Z., Wu, C., Xie, F., Slysz, G. W., Tolic, N., Monroe, M. E., Petyuk, V. A., Payne, S. H., Fujimoto, G. M., Moore, R. J., Fillmore, T. L., Schepmoes, A. A., Levine, D. A., Townsend, R. R., Davies, S. R., Li, S., Ellis, M., Boja, E., Rivers, R., ... Smith, R. D. (2015). Comprehensive quantitative analysis of ovarian and breast cancer tumor peptidomes. Journal of Proteome Research, 14(1), 422-433. https://doi.org/10.1021/pr500840w