In an effort to circumvent the limitations associated with biomarker discovery workflows involving cell lines and cell cultures, histology-directed MALDI protein profiling and imaging mass spectrometry will be used for identification of vascular endothelial biomarkers suitable for early prostate cancer detection by CEUS targeted molecular imaging
Aim 1. To characterize tumor neovasculature biomarker expression patterns in malignant prostate tissues and identify imaging biomarkers. We will use histology-directed protein profiling to acquire tumor neovasculature specific biomarker expression patterns associated with malignant prostate tissues. Protein profiles will be acquired by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Specifically, we will acquire composite protein profiles from vascular endothelial cells, adenocarcinoma cells and adjacent normal cells from radical prostatectomy tissue samples and exploit principal component analysis and other statistical methods to develop a ranked list of protein masses that best differentiate tumor associated vascular endothelial cells from other cells. To confirm our initial findings, a vascular endothelial cell specific protein classifier will be used to characterize a blinded set of prostatectomy
tissue samples with respect to the presence of tumor neovasculature. Newly discovered candidate imaging biomarkers will be further evaluated in Aim 2.
Aim 2. To validate tumor neovasculature biomarkers in malignant prostate tissues by multiple reaction monitoring mass spectrometry. We will use multiple reaction monitoring (MRM) and stable isotope dilution (SID) mass spectrometry to quantitate expression levels of newly identified and existing tumor neovasculature biomarkers including VEGFR2, αvβ3-integrin, Thy1, CD276 and PSMA. Over the course of the
Gambhir/Brooks Set-Aside Proposal 2 validation study, we will evaluate the 80 prostate tissues acquired in conjunction with Aim 1 and a further 60 well annotated prostate tissues acquired from Stanford and our EDRN collaborators.
There are currently no biomarkers annotated for this protocol.
No datasets are currently associated with this protocol.
The National Cancer Institute's Division of Cancer Prevention has released a new funding opportunity to solicit organ-specific applications for Biomarker Developmental Laboratories (BDLs), one of the four scientific units of the recently funded Early Detection Research Network (EDRN). The EDRN is a national infrastructure funded to discover, develop, and validate biomarkers for risk assessment, detection, and molecular diagnosis and prognosis of early cancer. BDLs are responsible for the discovery, development, characterization, and testing of new, or the refinement of existing, biomarkers and biomarker assays for risk assessment, detection, and molecular diagnosis and prognosis of cancers.
The existing BDLs are primarily focused on ovary and gastrointestinal cancers. The proposed BDLs (to be supported under this funding opportunity) should be focused on one or more of the following cancers: breast, prostate and other genitourinary organs, or lung. In addition, cancers with rapidly rising incidence rates, e.g., endometrial, hepatocellular, kidney, thyroid, oropharyngeal cancers, and/or cancers with unique etiology, e.g., mesothelioma, will be considered.
The newly funded units of the Early Detection Research Network will be announced later in April. Successful applicants have already been notified. Those researchers who were not successful during the last round of applications are encouraged to apply to this opportunity.