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 Communjournal_title
Nature communicationsauthors
Latonen L,Afyounian E,Jylhä A,Nättinen J,Aapola U,Annala M,Kivinummi KK,Tammela TTL,Beuerman RW,Uusitalo H,Nykter M,Visakorpi Tdoi
10.1038/s41467-018-03573-6subject
Has Abstractpub_date
2018-03-21 00:00:00pages
1176issue
1issn
2041-1723pii
10.1038/s41467-018-03573-6journal_volume
9pub_type
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