Proteome Characterization Center: A Genoproteomics Pipeline for Cancer Biomarkers
Molecular characterization of human cancers has generated large volumes of genomic data through
comprehensive and coordinated efforts such as The Cancer Genome Atlas (TCGA) Project. However, the
mechanisms by which alterations of these cancer genes singly or cooperatively transform cells remain poorly
understood. The overarching hypothesis of our PCC is that genomic data provides a highly valuable
molecular draft toward the identification of genes and pathways that potentially could be useful for discovery of
cancer biomarkers. The proteomic characterization of cancer tissues and plasma samples with genomic data
represent the key step not only to verify the genomic alterations at the protein level but also allow for the
analysis of unique features that are inherent to proteins including post-translational modifications. In addition,
these protein features are likely detected in body fluids by direct measurement of these secreted or otherwise
leaked proteins or by the body's immune response to the tumor antigens that can be used as surrogate
markers for disease detection with minimum invasion.
The main goal of our Biomarker Discovery Unit is to comprehensively characterize tumor and normal
biospecimens and identify their protein composition in order to systematically identify and prioritize ovarian
cancer-related proteins for advancement to verification. The objectives of our Biomarker Verification Unit is to
develop quantitative and multiplex assays that are sensitive, accurate, and reproducible to verify ovarian
cancer candidate biomarkers identified and selected by the Biomarker Candidate Selection Subcommittee of
the CPTC and to verify them in tissue and plasma for their potential as biomarkers to detect ovarian cancer
early and/or to discriminate malignant from benign ovarian tumors. It is expected that the verified proteins from
this proposal will provide a repertoire of new biomarkers for future clinical and translational studies to
determine their clinical utility. To achieve these goals, we have proposed a proteomic technology pipeline
consisting of protein microarray and mass spectrometry-based methods developed or established by our
internationally known investigators in our team to characterize proteins from genetic mutations,
rearrangements, gene expression, post-translational modifications (phosphorylation, glycosylation, and
acetylation) as well as autoantibodies against cancer-specific protein changes. In addition, the proteomics
investigators will work with our multidisciplinary team of scientists and clinicians that includes experts in clinical
oncology, clinical chemistry, cancer biology, genomics, bioinformatics, biostatistics, experimental design,
metrology/standards, technology optimization, assay construction, and project management for the
development of biomarkers with specific clinical utilities for ovarian cancer.
We propose six specific aims:
1. Conduct technologically advanced, comprehensive, and rigorous characterization of proteins in
biospecimens provided by the CPTC Resource Center in order to identify proteins and modified proteins
(proteins from mutated or rearranged genes and post-translational modifications including phosphorylation,
glycosylation, and acetylation) in cancer tissues. [Discovery].
2. Prioritize the candidate proteins for their ability to detect ovarian cancer early and/or to distinguish ovarian
cancer from benign pelvic masses using an independent set of tissue specimens from our PCC.
Furthermore, plasma from matched PCC samples will be used to identify auto-antibodies that recognize
the altered cancer-associated proteins. [Discovery].
3. Establish systematic, comprehensive data analysis criteria for selection and prioritization of ovarian cancerrelated
proteins and their alterations for verification using integrated bioinformatics approaches that
incorporate existing knowledge, databases, and literature references in the selection process. [Discovery].
4. Systematically develop verification assays against protein targets identified and selected by the Biomarker
Candidate Selection Subcommittee. [Verification].
5. Apply the multiplex verification assays in plasma specimens to evaluate the clinical performance of the
markers for the early detection of ovarian cancer and/or discrimination of malignant from benign tumors. [Verification]
6. Develop proteomic technologies and bioinformatics tools for biomarker discovery and verification. [Both].
©2004, Computational Bioinformatics and Bioimaging Laboratory
(CBIL), Advanced Research Institute, Virginia Tech.
Updated: 04/02/2011. Suggestions/Comments