title: Comprehensive quantitative analysis of ovarian and breast cancer tumor peptidomes.
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.
authors.affiliation: Biological Sciences Division and ‡Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory , Richland, Washington 99354, United States.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Xu
authors.forename: Chaochao
authors.initials: C
authors.lastname: Wu
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Slysz
authors.forename: Nikola
authors.initials: N
authors.lastname: Tolic
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Monroe
authors.forename: Vladislav A
authors.initials: VA
authors.lastname: Petyuk
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Payne
authors.forename: Grant M
authors.initials: GM
authors.lastname: Fujimoto
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Moore
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Fillmore
authors.forename: Athena A
authors.initials: AA
authors.lastname: Schepmoes
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: R Reid
authors.initials: RR
authors.lastname: Townsend
authors.forename: Sherri R
authors.initials: SR
authors.lastname: Davies
authors.forename: Shunqiang
authors.initials: S
authors.lastname: Li
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellis
authors.forename: Emily
authors.initials: E
authors.lastname: Boja
authors.forename: Robert
authors.initials: R
authors.lastname: Rivers
authors.forename: Henry
authors.initials: H
authors.lastname: Rodriguez
authors.forename: Karin D
authors.initials: KD
authors.lastname: Rodland
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002853:Chromatography, Liquid; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D010455:Peptides; D020543:Proteome
keywords: breast cancer; ischemia; ovarian cancer; peptidomics; proteases; protein degradation; tumor