Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 16, Issue 4, Pages -Publisher
WILEY
DOI: 10.15252/msb.20199247
Keywords
OXPHOS; PDK4; prostate cancer; STAT3; TCA cycle
Categories
Funding
- COMET Competence Center CBmed-Center for Biomarker Research in Medicine [FA791A0906.FFG]
- Austrian Federal Ministry for Transport, Innovation and Technology (BMVIT)
- Austrian Federal Ministry for Digital and Economic Affairs (BMDW)
- Land Steiermark (Department 12, Business and Innovation)
- Styrian Business Promotion Agency (SFG)
- Vienna Business Agency
- FWF [P26011]
- Christian Doppler Laboratory for Applied Metabolomics
- Austrian Federal Ministry for Transport, Innovation and Technology
- National Foundation for Research, Technology and Development
- Austrian Science Fund (FWF) [W1213] Funding Source: Austrian Science Fund (FWF)
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Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co-expression network of transcriptomics data in addition to laser-microdissected proteomics from human and murine prostate FFPE samples. We show up-regulation of oxidative phosphorylation (OXPHOS) in PCa on the transcriptomic level and up-regulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression. We hereby identify gene expression of pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging, and PSA level. Therefore, low PDK4 is a promising marker for PCa with dismal prognosis.
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