Associate Laboratory i4HB - Institute for Health and Bioeconomy, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
UCIBIO/REQUIMTE, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
J Proteome Res. 2022 Mar 4;21(3):727-739. doi: 10.1021/acs.jproteome.1c00754. Epub 2021 Nov 23.
Prostate cancer (PCa) is a global health problem that affects millions of men every year. In the past decade, metabolomics and related subareas, such as lipidomics, have demonstrated an enormous potential to identify novel mechanisms underlying PCa development and progression, providing a good basis for the development of new and more effective therapies and diagnostics. In this study, a multiplatform metabolomics and lipidomics approach, combining untargeted mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based techniques, was applied to PCa tissues to investigate dysregulations associated with PCa development, in a cohort of 40 patients submitted to radical prostatectomy for PCa. Results revealed significant alterations in the levels of 26 metabolites and 21 phospholipid species in PCa tissue compared with adjacent nonmalignant tissue, suggesting dysregulation in 13 metabolic pathways associated with PCa development. The most affected metabolic pathways were amino acid metabolism, nicotinate and nicotinamide metabolism, purine metabolism, and glycerophospholipid metabolism. A clear interconnection between metabolites and phospholipid species participating in these pathways was observed through correlation analysis. Overall, these dysregulations may reflect the reprogramming of metabolic responses to produce high levels of cellular building blocks required for rapid PCa cell proliferation.
前列腺癌（PCa）是一个全球性的健康问题，每年影响着数以百万计的男性。在过去的十年中，代谢组学及其相关领域（如脂质组学）已经显示出巨大的潜力，可以识别前列腺癌发展和进展的新机制，为新的、更有效的治疗方法和诊断方法的发展提供了良好的基础。在这项研究中，采用了一种多平台代谢组学和脂质组学方法，结合非靶向质谱（MS）和基于核磁共振（NMR）的技术，应用于前列腺癌组织，以研究与前列腺癌发展相关的失调，该研究纳入了 40 名接受根治性前列腺切除术治疗前列腺癌的患者。结果表明，与相邻的非恶性组织相比，前列腺癌组织中 26 种代谢物和 21 种磷脂的水平发生了显著变化，这表明与前列腺癌发展相关的 13 种代谢途径发生了失调。受影响最严重的代谢途径是氨基酸代谢、烟酸和烟酰胺代谢、嘌呤代谢和甘油磷脂代谢。通过相关分析观察到参与这些途径的代谢物和磷脂之间存在明显的相互联系。总的来说，这些失调可能反映了代谢反应的重新编程，以产生大量用于快速前列腺癌细胞增殖的细胞构建块。
