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.

中文翻译：

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STAT3 依赖性分析表明 PDK4 是前列腺癌复发的独立预测因子。

前列腺癌 (PCa) 具有广泛的临床行为；因此，迫切需要生物标志物进行风险分层。在这里，我们的目标是通过利用转录组数据的基因共表达网络以及来自人类和小鼠前列腺 FFPE 样本的激光显微切割蛋白质组学来寻找潜在的风险分层生物标志物。我们在转录组水平上显示 PCa 中氧化磷酸化 (OXPHOS) 的上调，在蛋白质组水平上显示 TCA 循环/OXPHOS 的上调，这与 STAT3 表达呈负相关。我们特此确定丙酮酸脱氢酶激酶 4 (PDK4)（TCA 循环的关键调节因子）的基因表达是 PCa 中一个有前景的独立预后标志物。PDK4 预测疾病复发，独立于分级、分期和 PSA 水平等诊断风险因素。因此，低 PDK4 是预后不良的 PCa 的一个有前途的标志物。