Identification of Cancer-Specific Glycoproteins in Triple-Negative Breast Cancer
LH Tseng, P Argani, Y Li, Y Tian, MF Lopez, D Sarracino, T Rezai, M Athanas, B Krastins, DW Chan, H Zhang. Johns Hopkins Medical Institutions, Baltimore; Thermo Fisher Scientific, Cambridge, MA; VAST Scientific, Cambridge, MA
Background: Breast cancer is a heterogeneous group of tumors and can be subdivided into subtypes on the basis of expression of estrogen receptor (ER) and progesterone receptor (PR) and HER2 gene amplification. The expression patterns of these growth factor receptors (GFRs) are the key prognosis factors for breast cancer therapy such as hormone therapy, biological therapy, or chemotherapy. Breast cancer without ER, PR, and Her2 expression (Triple-negative breast cancer, TNBC) is associated with more aggressive clinical courses, limited treatment options, and worse clinical outcomes. Patients with TNBC are insensitive to anti-estrogen or anti-HER2 therapy. Over expression of other cell surface proteins and increased signaling of other GFRs have been indicated to contribute to the resistance. Identification and better understanding of cell surface proteins over expressed in TNBC could be used to develop or guide novel therapies and improve clinical outcomes.
Design: Proteins exposed to extracellular environments are mostly glycosylated; therefore we isolate glycoproteins using solid-phase extraction of glycopeptides from TNBC and patient-matched non-cancer tissues. The isolated glycopeptides were analyzed by LTQ and LTQ Orbitrap mass spectrometers and quantified by automated label-free differential expression software, SIEVE. Over expression of cell surface proteins were further verified by selective reaction monitoring (SRM), Western blot analyses, and/or immunohistochemistry.
Results: Five patient-matched TNBC and non-cancer controls were analyzed. 313 glycopeptides from 145 glycoproteins were identified. Candidate glycoproteins with biological significance were found to have increased expression in cancer tissues. In the future, larger number of specimens will be used to validate these findings.
Conclusions: This study identified over a hundred potential glycoproteins over expressed in TNBC using glycoproteomic approach. These proteins may be potential candidate biomarkers for targeted therapy in this special group of breast cancer patients.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 34, Tuesday Afternoon