ToPCaP

Protein expression profiles of morphologically discrete foci in prostate cancer

Protein expression profiles of morphologically discrete foci in prostate cancer

The project aims are to undertake a highly focused proteomics discovery strategy designed to meet one of the most significant clinical issues in the treatment of prostate cancer. This is the detection, as early as possible, of those patients who are most likely to continue disease progression after radical prostatectomy. Working in collaboration with the Irish Prostate Cancer Research Consortium (PCRC), using high quality patient tissue samples, we will investigate differences in the protein expression profiles of morphologically discrete regions in the tumor tissue of radical prostatectomy patients in order to discriminate between Gleason scores 3+4 and 4+3 with an aim to discover and develop biomarkers of advanced disease. To do this will we investigate the hypothesis that the analysis of protein expression in tumors of Gleason score 3+4 versus 4+3 will allow us to generate a map of protein expression changes during the development of the disease.

Our objectives are:

· To use lasers to capture microdissection to isolate discrete regions of prostate cancer tumors in tissue sections obtained from radical prostatectomy patients belonging to the PCRC.

· To use label-free LC-MS/MS to characterize in detail the protein expression profiles of defined tumor regions.

· To apply appropriate statistical tools to the MS data to a) develop an overview of protein expression differences, b) identify pathways that are active in these tumor regions, c) identify key peptides/proteins that discriminate between different Gleason scores, d) develop multiplexed quantitative MRM assays to the peptide/protein candidates and use these assays to undertake initial measurements in patient tissue/serum samples in order to validate the findings.