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, and 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 post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Additionally, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. In conclusion, peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

Authors:

Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas A. ^[1]; Townsend, R. Reid ^[2]; Davies, Sherri R. ^[2]; Li, Shunqiang ^[2]; Ellis, Matthew ^[2]; Boja, Emily ^[3]; Rivers, Robert ^[3]; Rodriguez, Henry ^[3] more »; Rodland, Karin D.; Liu, Tao; Smith, Richard D. « less

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+ Show Author Affiliations

1. Gynecology Service/Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States
2. Department of Medicine, Washington University, St. Louis, Missouri 63130, United States
3. Office of Cancer Clinical Proteomics Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States

Publication Date:

Mon Nov 10 00:00:00 EST 2014

Research Org.:

Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)

Sponsoring Org.:

USDOE; US Dept. of Defense (DOD)

OSTI Identifier:

1163621

Alternate Identifier(s):

OSTI ID: 1171275

Report Number(s):

PNNL-SA-103951
Journal ID: ISSN 1535-3893

Grant/Contract Number:  

AC05-76RL01830; U24CA160019; P41GM103493; MIPR2DO89M2058

Resource Type:

Published Article

Journal Name:

Journal of Proteome Research

Additional Journal Information:

Journal Name: Journal of Proteome Research Journal Volume: 14 Journal Issue: 1; Journal ID: ISSN 1535-3893

Publisher:

American Chemical Society

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; protein degradation; peptidomics; proteases; tumor; ovarian cancer; breast cancer; ischemia; Environmental Molecular Sciences Laboratory