Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Prostate. 2021 Feb;81(3):157-169. doi: 10.1002/pros.24092. Epub 2020 Dec 18.
The Warburg effect seen in most solid tumors occurs only in the late stages of prostate cancer (PCa). Currently, the management of patients with low-risk localized PCa and patients after radical therapy remains a challenge. Our objective here was to evaluate glycometabolism-related genes as prognostic signatures for PCa.
The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases and glycometabolism-related gene sets were obtained online. Glycometabolic prognostic signatures were identified and validated in a TCGA cohort and tested in an ICGC cohort. We used the gene set enrichment analysis to reveal biological processes associated with the glycometabolism-related signatures. Novel glycometabolism-related genes were selected for verifying their oncogenic phenotypes in vitro.
Two glycometabolic prognostic signatures were applied respectively to construct risk score formulas for PCa. Survival and receiver operating characteristic curve analyses were performed to detect the value of these prognostic signatures. We performed univariate and multivariate Cox regression analyses in the TCGA cohort, demonstrating the independence of the prognostic signatures. Three glycometabolism-related genes were found to be novel PCa-associated genes. These were shown to affect proliferation, cell cycle progression, and glycolysis of DU145 and PC3 cells in different degrees.
The present research represents the first glycometabolic and high-throughput investigation on PCa, revealing potential biomarkers and treatment targets. We confirm the vital role of glycometabolism in PCa and provide essential resources for future exploration of metabolism in PCa.
大多数实体瘤中观察到的沃伯格效应仅出现在前列腺癌（PCa）的晚期。目前，低危局限性 PCa 患者和根治性治疗后患者的管理仍然是一个挑战。我们的目的是评估糖代谢相关基因作为 PCa 的预后标志物。
在线获取国际癌症基因组联盟（ICGC）和癌症基因组图谱（TCGA）数据库以及糖代谢相关基因集。在 TCGA 队列中识别和验证糖代谢预后特征，并在 ICGC 队列中进行测试。我们使用基因集富集分析来揭示与糖代谢相关特征相关的生物学过程。选择新的糖代谢相关基因在体外验证其致癌表型。
分别应用两个糖代谢预后特征来构建用于 PCa 的风险评分公式。进行生存和接收者操作特征曲线分析以检测这些预后特征的价值。我们在 TCGA 队列中进行了单因素和多因素 Cox 回归分析，证明了预后特征的独立性。发现三个糖代谢相关基因是新的与 PCa 相关的基因。这些基因在不同程度上影响 DU145 和 PC3 细胞的增殖、细胞周期进程和糖酵解。
本研究代表了对 PCa 的首次糖代谢和高通量研究，揭示了潜在的生物标志物和治疗靶点。我们证实了糖代谢在 PCa 中的重要作用，并为未来探索 PCa 中的代谢提供了必要的资源。
