The overall goal of this project is to identify autoantibody biomarkers in sera that can be readily used for the early detection of cancer. Antibodies are induced by tumor-specific alterations in protein expression, mutation, degradation, or localization, with high specificity. We have developed a novel programmable protein microarray technology (NAPPA), which uses printed cDNA encoding tumor antigens that are translated in vitro. We have been funded for the past four years as an EDRN Biomarker Development Laboratory to develop NAPPA as a clinical research tool and to employ it for the detection of autoantibody biomarkers for breast cancer, and have screened over 700 sera and identified 32 novel breast and 23 ovarian biomarkers that have undergone blinded validation studies. Here, we propose to increase the feature density of NAPPA arrays in order to accommodate the increasing size of our cDNA collection, which now approaches 10,000 unique genes (Aim 1) and to develop a method for producing glycoproteome arrays (Aim 2). Both of these methods will enhance autoantibody biomarker discovery by increasing the number and quality of the antigens screened.
Aim 3 will use the results of Aims 1 and 2 to expand the top breast cancer biomarkers that have been identified to focus on particular subtypes of breast cancer that are more difficult to detect including Her2+ breast cancers, triple-negative (ER-PR-Her2-) breast cancers, and cancers that occur in the setting of high breast density. Association of antibody detection and tumor antigen expression will be explored.
Aim 4 will assess the performance characteristics of the combined set of top breast cancer biomarkers in Phase II studies using sera collected in multicenter clinical studies.
Aim 5 will focus on the utility of these biomarkers to detect disease prior to clinical diagnosis. At the end of these experiments, our goal is to identify autoantibody serum signatures that can be used by EDRN CEVCs in further Phase III independent validation studies for the early detection of breast cancer according to the EDRN biomarker discovery guideline.

Public Health Relevance

In 2008, it is estimated that over 40,000 people will die of breast cancer, and over 500,000 will die of other cancers, with increased morbidity and mortality when cancers are detected at late stages. This project focuses on eariy detection biomarker discovery for breast cancer to complement mammographic screening, with an ultimate goal to reduce overall breast cancer morbidity and mortality.

Agency
National Institute of Health (NIH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA117374-10
Application #
8706682
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Patriotis, Christos F
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Miscellaneous
Type
Organized Research Units
DUNS #
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Katchman, Benjamin A; Smith, Joseph T; Obahiagbon, Uwadiae et al. (2016) Application of flat panel OLED display technology for the point-of-care detection of circulating cancer biomarkers. Sci Rep 6:29057
Ewaisha, Radwa; Gawryletz, Chelsea D; Anderson, Karen S (2016) Crucial considerations for pipelines to validate circulating biomarkers for breast cancer. Expert Rev Proteomics 13:201-11
Yu, Xiaobo; Petritis, Brianne; LaBaer, Joshua (2016) Advancing translational research with next-generation protein microarrays. Proteomics 16:1238-50
Yu, Xiaobo; LaBaer, Joshua (2015) High-throughput identification of proteins with AMPylation using self-assembled human protein (NAPPA) microarrays. Nat Protoc 10:756-67
Anderson, Karen S; Cramer, Daniel W; Sibani, Sahar et al. (2015) Autoantibody signature for the serologic detection of ovarian cancer. J Proteome Res 14:578-86
Dahlstrom, Kristina R; Anderson, Karen S; Cheng, Julia N et al. (2015) HPV Serum Antibodies as Predictors of Survival and Disease Progression in Patients with HPV-Positive Squamous Cell Carcinoma of the Oropharynx. Clin Cancer Res 21:2861-9
Wang, Jie; Figueroa, Jonine D; Wallstrom, Garrick et al. (2015) Plasma Autoantibodies Associated with Basal-like Breast Cancers. Cancer Epidemiol Biomarkers Prev 24:1332-40
Anderson, Karen S; Gerber, Jennifer E; D'Souza, Gypsyamber et al. (2015) Biologic predictors of serologic responses to HPV in oropharyngeal cancer: The HOTSPOT study. Oral Oncol 51:751-8
Anderson, Karen S; Dahlstrom, Kristina R; Cheng, Julia N et al. (2015) HPV16 antibodies as risk factors for oropharyngeal cancer and their association with tumor HPV and smoking status. Oral Oncol 51:662-7
Marks, Jeffrey R; Anderson, Karen S; Engstrom, Paul et al. (2015) Construction and analysis of the NCI-EDRN breast cancer reference set for circulating markers of disease. Cancer Epidemiol Biomarkers Prev 24:435-41

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