Men with African ancestry are more likely to develop aggressive prostate cancer (PCa) and to die from this disease. The study of PCa in the South African population represents an opportunity for biomedical research due to the high prevalence of aggressive PCa. While inflammation is known to play a significant role in PCa progression, its association with tumor stage in populations of African descent has not been explored in detail. Identification of new metabolic biomarkers of inflammation may improve diagnosis of patients with aggressive PCa. Plasma samples were profiled from 41 South African men with PCa using nuclear magnetic resonance (NMR) spectroscopy. A total of 41 features, including metabolites, lipid classes, total protein, and the inflammatory NMR markers, GlycA, and GlycB, were quantified from each NMR spectrum. The Bruker’s B.I.-LISA protocols were used to characterize 114 parameters related to the lipoproteins. The unsupervised KODAMA method was used to stratify the patients of our cohort based on their metabolic profile. We found that the plasma of patients with very high risk, aggressive PCa and high level of C-reactive protein have a peculiar metabolic phenotype (metabotype) characterized by extremely high levels of GlycA and GlycB. The inflammatory processes linked to the higher level of GlycA and GlycB are characterized by a deep change of the plasma metabolome that may be used to improve the stratification of patients with PCa. We also identified a not previously known relationship between high values of VLDL and low level of GlycB in a different metabotype of patients characterized by lower-risk PCa. For the first time, a portrait of the metabolic changes in African men with PCa has been delineated indicating a strong association between inflammation and metabolic profiles. Our findings indicate how the metabolic profile could be used to identify those patients with high level of inflammation, characterized by aggressive PCa and short life expectancy. Integrating a metabolomic analysis as a tool for patient stratification could be important for opening the door to the development of new therapies. Further investigations are needed to understand the prevalence of an inflammatory metabotype in patients with aggressive PCa.

中文翻译：

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南非前列腺癌患者的炎症代谢特征

具有非洲血统的男性更有可能患上侵袭性前列腺癌 (PCa) 并死于这种疾病。由于侵袭性 PCa 的流行，南非人群中 PCa 的研究为生物医学研究提供了机会。虽然已知炎症在 PCa 进展中起着重要作用，但尚未详细探讨其与非洲后裔人群肿瘤分期的关联。鉴定新的炎症代谢生物标志物可能会改善侵袭性 PCa 患者的诊断。使用核磁共振 (NMR) 光谱分析了来自 41 名患有 PCa 的南非男性的血浆样本。从每个 NMR 谱中量化了总共 41 个特征，包括代谢物、脂质类别、总蛋白和炎症 NMR 标记物 GlycA 和 GlycB。布鲁克的 BI -LISA 协议用于表征与脂蛋白相关的 114 个参数。无监督的 KODAMA 方法用于根据他们的代谢特征对我们队列中的患者进行分层。我们发现具有极高风险、侵袭性 PCa 和高水平 C 反应蛋白的患者的血浆具有特殊的代谢表型（代谢型），其特征是极高水平的 GlycA 和 GlycB。与较高水平的 GlycA 和 GlycB 相关的炎症过程的特征是血浆代谢组的深度变化，可用于改善 PCa 患者的分层。我们还发现，在以低风险 PCa 为特征的不同代谢型患者中，VLDL 的高值与 GlycB 的低水平之间存在一种以前未知的关系。首次，描绘了患有 PCa 的非洲男性的代谢变化，表明炎症和代谢特征之间存在很强的关联。我们的研究结果表明如何使用代谢特征来识别那些具有高炎症水平的患者，这些患者的特征是侵袭性 PCa 和预期寿命短。将代谢组学分析作为患者分层的工具对于打开新疗法开发的大门很重要。需要进一步研究以了解侵袭性 PCa 患者炎症代谢型的流行情况。特点是侵袭性 PCa 和预期寿命短。将代谢组学分析作为患者分层的工具对于打开新疗法开发的大门很重要。需要进一步研究以了解侵袭性 PCa 患者炎症代谢型的流行情况。特点是侵袭性 PCa 和预期寿命短。将代谢组学分析作为患者分层的工具对于打开新疗法开发的大门很重要。需要进一步研究以了解侵袭性 PCa 患者炎症代谢型的流行情况。