N-Glycoproteomics of Patient-Derived Xenografts: A Strategy to Discover Tumor-Associated Proteins in High-Grade Serous Ovarian Cancer

Ankit Sinha; Ali Hussain; Vladimir Ignatchenko; Alexandr Ignatchenko; Kwan Ho Tang; Victor W H Ho; Benjamin G Neel; Blaise Clarke; Marcus Q Bernardini; Laurie Ailles; Thomas Kislinger

doi:10.1016/j.cels.2019.03.011

N-Glycoproteomics of Patient-Derived Xenografts: A Strategy to Discover Tumor-Associated Proteins in High-Grade Serous Ovarian Cancer

Cell Syst. 2019 Apr 24;8(4):345-351.e4. doi: 10.1016/j.cels.2019.03.011. Epub 2019 Apr 10.

Authors

Affiliations

¹ University of Toronto, Department of Medical Biophysics, Toronto, ON M5G 1L7, Canada.
² Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
³ Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY 10016, USA.
⁴ Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY 10016, USA.
⁵ Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, ON M5S 1A8, Canada.
⁶ Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; University of Toronto, Department of Obstetrics and Gynaecology, Toronto, ON M5G 1E2, Canada.
⁷ University of Toronto, Department of Medical Biophysics, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
⁸ University of Toronto, Department of Medical Biophysics, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada. Electronic address: thomas.kislinger@utoronto.ca.

PMID: 30981729
DOI: 10.1016/j.cels.2019.03.011

Abstract

High-grade serous ovarian carcinoma (HGSC) is the most common and lethal subtype of gynecologic malignancy in women. The current standard of treatment combines cytoreductive surgery and chemotherapy. Despite the efficacy of initial treatment, most patients develop cancer recurrence, and 70% of patients die within 5 years of initial diagnosis. CA125 is the current FDA-approved biomarker used in the clinic to monitor response to treatment and recurrence, but its impact on patient survival is limited. New strategies for the discovery of HGSC biomarkers are urgently needed. Here, we describe a proteomics strategy to detect tumor-associated proteins in serum of HGSC patient-derived xenograft models. We demonstrate proof-of-concept applicability using two independent, longitudinal serum cohorts from HGSC patients.

Keywords: N-glycosylation; biomarker; ovarian cancer; patient-derived xenograft; serum proteomics; targeted proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers, Tumor / blood*
Carcinoma / blood*
Carcinoma / pathology
Cell Line, Tumor
Female
Glycomics / methods
Glycoproteins / blood*
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Ovarian Neoplasms / blood*
Ovarian Neoplasms / pathology
Proteomics / methods*

Substances

Biomarkers, Tumor
Glycoproteins

Grants and funding

MOP-133615/CIHR/Canada