Project

Stratifying Intermediate-Risk Prostate Cancer Subtypes by Complex-Centric Mass Spectrometry-based Proteome Analysis

Short Summary

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.

Goals

This research project seeks to compare the protein complex profiles of biopsies of favorable and unfavorable intermediate-risk PC in qualitative and quantitative terms, also searching for similarities and differences with control and high-grade PC samples, through a novel proteomic complex-centric experimental platform.

Significance

The molecular characterization of PC tissues could satisfy the need for PC classification into new risk-related subgroups and for new drug targets. The identification of structural perturbations of proteins in complexes of intermediate-risk PC samples, as proposed in this research project, could overcome the limitations of genomic studies, disclosing the whole picture of tumor etiology.

Background

Risk classification for prostate cancer (PC) is one of the challenges connected to this disease since it is known that within the same risk sub-categories diverse patient populations with highly variable outcomes and treatment responses exist. In particular, among these patient sub-groups, favorable and unfavorable intermediate-risk PC are the most difficult to stratify.

Transition Postdoc Fellowship Project

Consortium

Status

Completed

1st Call, TPdF