PDK4 Gene May Serve as Prognostic Marker in Prostate Cancer
Posted: Wednesday, July 8, 2020
According to Lukas Kenner, MD, of the Medical University of Vienna, and colleagues, signal transducer and activator of transcription 3 (STAT3), a prospective prostate cancer tumor suppressor, appears to be a direct regulator of expression of the gene pyruvate dehydrogenase kinase 4 (PDK4). The findings, which were published in Molecular Systems Biology, suggest PDK4 may serve as a predictor of early biochemical recurrence of low‐/intermediate‐risk T1c–T2c prostate tumors, although further research is needed to implement it in clinical practice.
“We show upregulation of oxidative phosphorylation (OXPHOS) in prostate cancer on the transcriptomic level and upregulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression,” the investigators stated. “We hereby identify gene expression of PDK4, a key regulator of the TCA cycle, as a promising independent prognostic marker in prostate cancer.”
Prostate samples were collected from 84 patients with primary prostate cancer, and 7 patients with bladder cancer served as healthy prostate controls. The investigators conducted experiments using 19-week-old wild-type, Ptenpc−/−, and PtenStat3pc−/− mice, cell culture, data analyses, and several other tests to analyze the biologic mechanisms associated with STAT3 expression.
Based on proteomic analyses of human formalin-fixed paraffin-embedded tissue samples, the investigators determined that low STAT3 expression may be associated with high TCA/OXPHOS and thus tumor growth. TCA/OXPHOS upregulation was also observed in PtenStat3pc−/− mice, compared with the wild-type mice. PtenStat3pc−/− mice also exhibited significantly higher amounts of TCA metabolites such as pyruvate (P = .01), fumarate (P = .027), and malate (P = .029)—all suggestive of high TCA cycle activity. A significant downregulation of PDK4 was exhibited in low STAT3 samples, indicating PDK4 is likely regulated by STAT3 and may harness the potential to predict disease prognosis.
Disclosure: For full disclosures of the study authors, visit embopress.org.
