STAT3-dependent systems-level analysis reveals PDK4 to be associated with favorable outcome in primary prostate cancer.

Prostate cancer has a broad spectrum of clinical behavior, hence biomarkers are urgently needed for risk stratification. We previously described the protective effect of signal transducer and activator of transcription 3 (STAT3) in a prostate cancer mouse model. We now show the importance of STAT3-regulated metabolic functions and explain their influence on aggressive prostate cancer. By utilizing a gene co-expression network in addition to laser microdissected proteomics from human and murine FFPE samples, we established a workflow that facilitates the discovery of new biomarkers. We thereby identified the protective effect of pyruvate dehydrogenase kinase 4 (PDK4) in prostate cancer. PDK4 is a key regulator of the citrate cycle and low PDK4 is significantly associated with disease recurrence.