POSTTRANSLATIONAL MODIFICATIONS FOR EARLY DETECTION OF BREAST CANCER
EMSL Project ID
30428
Abstract
Breast cancer is the most common cancer in women and is the second leading cause of death due to cancer. The goal of this study is to use proteomics to identify post-translational modifications (PTMs) of circulating proteins that can be used for the early detection of breast cancer. There is considerable evidence that a variety of PTMs are altered in cancer, and that levels of circulating modified proteins are altered in response to cancer. These PTMs can be associated with disruption of normal biological processes, such as glycosylation, or due to modification resulting from elevated oxidative stress. One shortcoming of previous biomarker studies on circulating PTMs is that these studies either globally analyze levels of a particular PTM, without identifying what proteins are modified, or they target proteins that are unlikely to originate primarily from the breast. Since it is unlikely that these protein modifications are tissue specific, these markers are unlikely to be selective for breast cancer. We hypothesize that PTMs on proteins that are abundantly secreted by the breast will provide a sensitive and specific method for detecting breast cancer. In order to test this hypothesis, we will utilize a dual approach for discovering novel protein-specific PTMs in blood from breast cancer patients. Both approaches will use immunoprecipitation to increase the concentration and purity of the targeted proteins. The first approach (Aim #1) will undertake a combined top-down/bottom-up proteomic analysis of circulating proteins that are known to be secreted by the breast. This analysis will provide an unbiased evaluation of what PTMs can be identified on breast secretory proteins. The second approach (Aim #2) will analyze specific PTMs independent of protein sequence. This analysis will identify novel proteins with PTMs that are increased in cancer. We will use a meta-analysis of published DNA microarray studies to determine if the expression of these proteins is regulated by breast cancer.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2008-12-05
End Date
2009-12-06
Status
Closed
Released Data Link
Team
Principal Investigator
Related Publications
Jin H, and RC Zangar. 2010. "Antibody Microarrays for High-Throughput, Multianalyte Analysis." Cancer Biomarkers 6(5-6):281-290. doi:10.3233/CBM-2009-0140