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Using MALDI-IMS and MRM to stablish a pipeline for discovery and validation of tumor neovasculature biomarker candidates.

Gambhir, SanjivStanford University

No coordinating investigator defined.

No involved investigator sites defined.

Prostate and Urologic Cancers Research Group

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.

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