Integrative proteomics in prostate cancer uncovers robustness against genomic and transcriptomic aberrations during disease progression.

Abstract:

:To understand functional consequences of genetic and transcriptional aberrations in prostate cancer, the proteomic changes during disease formation and progression need to be revealed. Here we report high-throughput mass spectrometry on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration resistant prostate cancer (CRPC). Each sample group shows a distinct protein profile. By integrative analysis we show that, especially in CRPC, gene copy number, DNA methylation, and RNA expression levels do not reliably predict proteomic changes. Instead, we uncover previously unrecognized molecular and pathway events, for example, several miRNA target correlations present at protein but not at mRNA level. Notably, we identify two metabolic shifts in the citric acid cycle (TCA cycle) during prostate cancer development and progression. Our proteogenomic analysis uncovers robustness against genomic and transcriptomic aberrations during prostate cancer progression, and significantly extends understanding of prostate cancer disease mechanisms.

journal_name

Nat Commun

journal_title

Nature communications

authors

Latonen L,Afyounian E,Jylhä A,Nättinen J,Aapola U,Annala M,Kivinummi KK,Tammela TTL,Beuerman RW,Uusitalo H,Nykter M,Visakorpi T

doi

10.1038/s41467-018-03573-6

subject

Has Abstract

pub_date

2018-03-21 00:00:00

pages

1176

issue

1

issn

2041-1723

pii

10.1038/s41467-018-03573-6

journal_volume

9

pub_type

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