Early Breast Cancer Biomarkers Verification (PNNL Scope #47174, RD Smith's EIF project)
EMSL Project ID
38692
Abstract
Our overall objective for studies performed in Years 4 to 6 is to contribute to the assembly of a highly confident protein panel for the early detection of breast cancer by applying the PNNL-developed unique high throughput and high sensitivity biomarker verification platform to the large-scale analysis of case and control clinical specimens. The biomarker verification platform will perform quantitative monitoring of several hundreds of candidate protein biomarkers from a large number of patient samples, which will be an integrated part of the efforts for biomarker verification by the EIF Breast Cancer Biomarker Consortium. The anticipated end-results will be 10 to 25 finalized highly confident biomarkers to be used for clinical assay development and validation. Through effective interactions between PNNL and the Consortium labs this goal will be achieved, taking advantage of the sensitivity and throughput offered by the variety of platforms in the Consortium labs, by selecting and dividing the initial candidates for coordinated verification efforts. To these concerted efforts, the PNNL platform brings higher throughput and significantly greater sensitivity for the detection of low abundance biomarkers due to the integration of fully automated multi-column LC separations, novel immunoaffinity separations, two-stage gas-phase separations, and high efficiency electrospray ionization/ion transmission technologies. We aim for developing and optimizing multiple reaction monitoring (MRM) assays for up to 300 candidate biomarkers, and for identifying a small subset of high confidence candidates for subsequent clinical validation through a 2-phase study using large sample cohorts. Under Phase 1 we will screen up to 300 candidate biomarkers using 100 patient samples plus 100 matched control (normal and other cancer types) samples. In Phase 2 we propose to integrate the data from the entire Consortium and finalize the top 50 highest confidence biomarkers from the Phase 1 efforts. These top candidates will be validated by performing Consortium-wide cross-verification for further enhanced specificity and prediction power. PNNL plans to analyze 150 patient samples and 150 matched control samples in Phase 2 in addition to the Phase 1 efforts.
Project Details
Start Date
2010-04-27
End Date
2012-11-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Hossain M, DT Kaleta, EW Robinson, T Liu, R Zhao, JS Page, RT Kelly, RJ Moore, K Tang, DG Camp, II, W Qian, and RD Smith. 2011. "Enhanced Sensitivity for Selected Reaction Monitoring–Mass Spectrometry-based Targeted Proteomics using a Dual-Stage Electrodynamic Ion Funnel Interface ." Molecular & Cellular Proteomics. MCP 10(2):, doi:10.1074/mcp.M000062-MCP201