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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays
Cancer Research, Volume 66, No. 2, Year 2006
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Description
A noninvasive screening test would significantly facilitate early detection of epithelial ovarian cancer. This study used a combination of high-throughput selection and array-based serologic detection of many antigens indicative of the presence of cancer, thereby using the immune system as a biosensor. This high-throughput selection involved biopanning of an ovarian cancer phage display library using serum immunoglobulins from an ovarian cancer patient as bait. Protein macroarrays containing 480 of these selected antigen clones revealed 65 clones that interacted with immunoglobulins in sera from 32 ovarian cancer patients but not with sera from 25 healthy women or 14 patients having other benign or malignant gynecologic diseases. Sequence analysis data of these 65 clones revealed 62 different antigens. Among the markers, we identified some known antigens, including RCAS1, signal recognition protein-19, AHNAK-related sequence, nuclear autoantogenic sperm protein, Nijmegen breakage syndrome 1 (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gene product, eukaryotic initiation factor 5A, and casein kinase II, as well as many previously uncharacterized antigenic gene products. Using these 65 antigens on protein microarrays, we trained neural networks on two-color fluorescent detection of serum IgG binding and found an average sensitivity and specificity of 55% and 98%, respectively. In addition, the top 6 of the most specific clones resulted in an average sensitivity and specificity of 32% and 94%, respectively. This global approach to antigenic profiling, epitomics, has applications to cancer and autoimmune diseases for diagnostic and therapeutic studies. Further work with larger panels of antigens should provide a comprehensive set of markers with sufficient sensitivity and specificity suitable for clinical testing in high-risk populations. ©2006 American Association for Cancer Research.
Authors & Co-Authors
Lu, Karen H.
United States, Houston
The University of Texas Md Anderson Cancer Center
Fishman, David A.
United States, New York
Nyu Grossman School of Medicine
Tromp, Gerard C.
United States, Detroit
Wayne State University School of Medicine
Drəghici, Sorin
United States, Detroit
Barbara Ann Karmanos Cancer Institute
United States, Detroit
Wayne State University
Statistics
Citations: 197
Authors: 4
Affiliations: 6
Identifiers
Doi:
10.1158/0008-5472.CAN-04-2962
ISSN:
00085472
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Participants Gender
Female