Drug Discovery Unit, Instituto de Investigación Sanitaria La Fe, Valencia 46026, Spain.
Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología (FIVO), Valencia 46009, Spain.
J Proteome Res. 2020 Oct 2;19(10):4082-4092. doi: 10.1021/acs.jproteome.0c00493. Epub 2020 Sep 23.
Prostate cancer (PCa) is a hormone-dependent tumor characterized by an extremely heterogeneous prognosis. Despite recent advances in partially uncovering some of the biological processes involved in its progression, there is still an urgent need for identifying more accurate and specific prognostic procedures to differentiate between disease stages. In this context, targeted approaches, focused on mapping dysregulated metabolic pathways, could play a critical role in identifying the mechanisms driving tumorigenesis and metastasis. In this study, a targeted analysis of the nuclear magnetic resonance-based metabolomic profile of PCa patients with different tumor grades, guided by transcriptomics profiles associated with their stages, was performed. Serum and urine samples were collected from 73 PCa patients. Samples were classified according to their Gleason score (GS) into low-GS (GS < 7) and high-GS PCa (GS ≥ 7) groups. A total of 36 metabolic pathways were found to be dysregulated in the comparison between different PCa grades. Particularly, the levels of glucose, glycine and 1-methlynicotinamide, metabolites involved in energy metabolism and nucleotide synthesis were significantly altered between both groups of patients. These results underscore the potential of targeted metabolomic profiling to characterize relevant metabolic changes involved in the progression of this neoplastic process.
前列腺癌(PCa)是一种激素依赖性肿瘤,其预后具有极强的异质性。尽管最近在部分揭示其进展过程中涉及的一些生物学过程方面取得了进展,但仍迫切需要确定更准确和特定的预后程序,以区分疾病阶段。在这种情况下,针对代谢途径失调的靶向方法可能在确定驱动肿瘤发生和转移的机制方面发挥关键作用。在这项研究中,对不同肿瘤分级的前列腺癌患者进行了基于核磁共振的代谢组学图谱的靶向分析,并结合与肿瘤分期相关的转录组学图谱进行指导。从 73 名前列腺癌患者中采集了血清和尿液样本。根据他们的 Gleason 评分(GS)将样本分为低 GS(GS<7)和高 GS 前列腺癌(GS≥7)组。在不同前列腺癌分级之间的比较中,发现有 36 条代谢途径失调。特别是,两组患者之间能量代谢和核苷酸合成涉及的葡萄糖、甘氨酸和 1-甲基烟酰胺等代谢物水平明显改变。这些结果强调了靶向代谢组学分析在描述该肿瘤过程进展中涉及的相关代谢变化的潜力。