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

Leena Latonen, Ebrahim Afyounian, Antti Jylhä, Janika Nättinen, Ulla Aapola, Matti Annala, Kati K. Kivinummi, Teuvo T. L. Tammela, Roger W. Beuerman, Hannu Uusitalo, Matti Nykter () and Tapio Visakorpi ()
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Leena Latonen: University of Tampere
Ebrahim Afyounian: University of Tampere
Antti Jylhä: University of Tampere
Janika Nättinen: University of Tampere
Ulla Aapola: University of Tampere
Matti Annala: University of Tampere
Kati K. Kivinummi: University of Tampere
Teuvo T. L. Tammela: University of Tampere and Tampere University Hospital
Roger W. Beuerman: University of Tampere
Hannu Uusitalo: University of Tampere
Matti Nykter: University of Tampere
Tapio Visakorpi: University of Tampere

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03573-6

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