期刊
JOURNAL OF PROTEOME RESEARCH
卷 21, 期 3, 页码 727-739出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.1c00754
关键词
prostate cancer; tissue; metabolomics; lipidomics; metabolic pathways
资金
- FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI)
- Portuguese funds through FCT-Fundacao para a Ciencia e a Tecnologia [POCI-01-0145-FEDER-030388 -PTDC/SAU-SER/30388/2017, UIDP/04378/2020, UIDB/04378/2020]
- Associate Laboratory Institute for Health and Bioeconomy -i4HB [LA/P/0140/2020]
- FCT [SFRH/BD/123012/2016]
- University of Aveiro
- FCT/MCT [UIDB/50017/2020, UIDP/50017/2020, UIDB/50006/2020, LISBOA-01-0145-FEDER-402-022125]
- FEDER, within the PT2020 Partnership Agreement
- European Social Fund (ESF) [ALG-05-3559-FSE-000010]
- Social Security Budget (SSB) through the Algarve Regional Operational Program
- Centro2020, through FEDER [POCI-01-0145-FEDER-030962]
- Centro2020, through PT2020 [POCI-01-0145-FEDER-030962]
Prostate cancer is a global health problem. Metabolomics and lipidomics have the potential to identify new mechanisms underlying PCa development and progress, providing a basis for new and more effective therapies and diagnostics. This study found dysregulations in multiple metabolic pathways associated with PCa development, which may reflect reprogramming of metabolic responses to facilitate rapid proliferation of PCa cells.
Prostate cancer (PCa) is a global health problem that affects millions of men every year. In the past decade, metabolomics and related subareas, such as lipidomics, have demonstrated an enormous potential to identify novel mechanisms underlying PCa development and progression, providing a good basis for the development of new and more effective therapies and diagnostics. In this study, a multiplatform metabolomics and lipidomics approach, combining untargeted mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based techniques, was applied to PCa tissues to investigate dysregulations associated with PCa development, in a cohort of 40 patients submitted to radical prostatectomy for PCa. Results revealed significant alterations in the levels of 26 metabolites and 21 phospholipid species in PCa tissue compared with adjacent nonmalignant tissue, suggesting dysregulation in 13 metabolic pathways associated with PCa development. The most affected metabolic pathways were amino acid metabolism, nicotinate and nicotinamide metabolism, purine metabolism, and glycerophospholipid metabolism. A clear interconnection between metabolites and phospholipid species participating in these pathways was observed through correlation analysis. Overall, these dysregulations may reflect the reprogramming of metabolic responses to produce high levels of cellular building blocks required for rapid PCa cell proliferation.
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