Genomic technologies alone do not provide comprehensive insights into the phenotypic diversity of tumors cells and tissues. Proteins, through numerous signaling networks, control and catalyze the molecular mechanisms underlying diseases. The characterization of the protein interactions and their organization into higher order structures (protein ‘complexome’), allows obtaining important information about protein functions and the state of cellular system. In cancer tissues, the evaluation of perturbations in protein-protein complex interactions with respect to control samples can elucidate the effects of the multitude of genomic lesions and environmental influences on the disease. For this research project, a cohort of intermediate-risk, high-grade and control PC tissue samples will be used. For the complexome characterization, I will apply and optimize the experimental workflow designed in the host laboratory, consisting of the fractionation of protein complexes combined with tandem mass spectrometry analysis.
The powerful and innovative method proposed will allow to determine and validate interconnections between proteins occurring in intermediate risk-PC prostate cancer, thus generating comprehensive snapshots of the protein complex landscape, quantifying both individual proteins and protein complexes and all their possible variants (with their stoichiometry) within PC tumor tissues. The information obtained could be related to genotype alterations of the two different PC sub-categories.