Use of a single-chain antibody library for ovarian cancer biomarker discovery.

Publication Type:

Journal Article

Source:

Molecular & cellular proteomics : MCP, Volume 9, Issue 7, p.1449-60 (2010)

Keywords:

2010, Administration Division, Adult, Aged, Aged, 80 and over, Antibody Development Core Facility, Antigens, Neoplasm, Center-Authored Paper, Female, Flow Cytometry Core Facility, Gene Library, Humans, Middle Aged, Ovarian Neoplasms, Protein Array Analysis, Proteomics Core Facility, Public Health Sciences Division, Risk Factors, Scientific Imaging Core Facility, Shared Resources, Single-Chain Antibodies, Tumor Markers, Biological, Young Adult

Abstract:

The discovery of novel early detection biomarkers of disease could offer one of the best approaches to decrease the morbidity and mortality of ovarian and other cancers. We report on the use of a single-chain variable fragment antibody library for screening ovarian serum to find novel biomarkers for the detection of cancer. We alternately panned the library with ovarian cancer and disease-free control sera to make a sublibrary of antibodies that bind proteins differentially expressed in cancer. This sublibrary was printed on antibody microarrays that were incubated with labeled serum from multiple sets of cancer patients and controls. The antibodies that performed best at discriminating disease status were selected, and their cognate antigens were identified using a functional protein microarray. Overexpression of some of these antigens was observed in cancer serum, tumor proximal fluid, and cancer tissue via dot blot and immunohistochemical staining. Thus, our use of recombinant antibody microarrays for unbiased discovery found targets for ovarian cancer detection in multiple sample sets, supporting their further study for disease diagnosis.