STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer

Mol Syst Biol. 2020 Apr;16(4):e9247. doi: 10.15252/msb.20199247.


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.

Keywords: OXPHOS; PDK4; STAT3; TCA cycle; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laser Capture Microdissection
  • Male
  • Mice
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology*
  • Oxidative Phosphorylation
  • Prognosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proteomics / methods*
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase / genetics*
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase / metabolism
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism
  • Systems Biology
  • Young Adult


  • Biomarkers, Tumor
  • PDK4 protein, human
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • STAT3 Transcription Factor
  • STAT3 protein, human