Proteomic Landscape of Prostate Cancer: The View Provided by Quantitative Proteomics, Integrative Analyses, and Protein Interactomes

Abstract

Prostate cancer is the second most frequent cancer of men worldwide. While the genetic landscapes and heterogeneity of prostate cancer are relatively well-known already, methodological developments now allow for studying basic and dynamic proteomes on a large scale and in a quantitative fashion. This aids in revealing the functional output of cancer genomes. It has become evident that not all aberrations at the genetic and transcriptional level are translated to the proteome. In addition, the proteomic level contains heterogeneity, which increases as the cancer progresses from primary prostate cancer (PCa) to metastatic and castration-resistant prostate cancer (CRPC). While multiple aspects of prostate adenocarcinoma proteomes have been studied, less is known about proteomes of neuroendocrine prostate cancer (NEPC). In this review, we summarize recent developments in prostate cancer proteomics, concentrating on the proteomic landscapes of clinical prostate cancer, cell line and mouse model proteomes interrogating prostate cancer-relevant signaling and alterations, and key prostate cancer regulator interactomes, such as those of the androgen receptor (AR). Compared to genomic and transcriptomic analyses, the view provided by proteomics brings forward changes in prostate cancer metabolism, post-transcriptional RNA regulation, and post-translational protein regulatory pathways, requiring the full attention of studies in the future.

Proteomic-based stratification of intermediate-risk prostate cancer patients

“…Our results both complement and extend upon recent proteomic studies in PCa 27 . The novel contribution of our work is first in presenting a substantially larger cohort size (n = 278) than previous studies, which typically comprise <100 patients 27 . Second, our study is able to identify potential novel therapeutic targets and build a prognostic signature that is completely independent of the GG, with the ability to identify patients at higher risk of developing BCR within the relatively indolent GG2.…”

From Omics to Multi-Omics Approaches for In-Depth Analysis of the Molecular Mechanisms of Prostate Cancer

“…Procedures for relative and absolute quantification have now been established. Current developments include reverse-phase protein microarrays, which warrant precise comparisons between healthy, diseased and treated tissues [ 194 ]. In addition, post-translational protein modifications, such as phosphorylation, ubiquitylation or glycosylation, are now likewise being investigated at a broad scale [ 195 ].…”

“…Proteome study of prostate cancer models grown in vitro or in vivo has been fruitful to gain insights into causal modifications related to treatment response and resistance [ 194 ]. Large-scale investigation of different androgen-dependent and -independent cell lines allowed researchers to find proteins linked to tumor progression and aggressiveness [ 196 , 197 ].…”

“…Concerning large-scale proteomic studies of clinical samples, a number of observations are now published [ 194 ]. The overlap among studies addressing primary tumors is, however, only partial, but proteins involved in metabolomic pathways, chiefly fatty acid synthesis, show consistent up-regulation.…”

“…However, as mentioned above, the correlation of genomic, transcriptomic and proteomic data originating from prostate cancer patient samples is often limited. Proteomic changes taking place during prostate cancer progression are not reliably predicted by gene copy numbers, DNA methylation or transcript abundance, especially in advanced tumors [ 194 ]. Indeed, detailed proteomic evaluation of clinical samples already allowed researchers to unravel the role of pathways previously not predicted to be involved in prostate cancer by alternative omics methods [ 204 ].…”