UCIBIO/REQUIMTE, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Cancer Biology & Epigenetics Group, Research Center (CI-IPOP) Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.
Sci Rep. 2018 Apr 3;8(1):5539. doi: 10.1038/s41598-018-23847-9.
Serum prostate-specific antigen (PSA) is currently the most used biomarker in clinical practice for prostate cancer (PCa) detection. However, this biomarker has several drawbacks. In this work, an untargeted gas chromatography-mass spectrometry (GC-MS)-based metabolomic profiling of PCa cells was performed to prove the concept that metabolic alterations might differentiate PCa cell lines from normal prostate cell line. For that, we assessed the differences in volatile organic compounds (VOCs) profile in the extracellular medium (exometabolome) of four PCa cell lines and one normal prostate cell line at two pH values (pH 2 and 7) by GC-MS. Multivariate analysis revealed a panel of volatile metabolites that discriminated cancerous from normal prostate cells. The most altered metabolites included ketones, aldehydes and organic acids. Among these, we highlight pentadecane-2-one and decanoic acid, which were significantly increased in PCa compared to normal cells, and cyclohexanone, 4-methylheptan-2-one, 2-methylpentane-1,3-diol, 4-methylbenzaldehyde, 1-(3,5-dimethylfuran-2-yl)ethanone, methyl benzoate and nonanoic acid, which were significantly decreased in PCa cells. The PCa volatilome was markedly influenced by the VOCs extraction pH, though the discriminant capability was similar. Overall, our data suggest that VOCs monitoring has the potential to be used as a PCa screening methodology.
血清前列腺特异性抗原(PSA)目前是临床用于前列腺癌(PCa)检测的最常用生物标志物。然而,这种生物标志物有几个缺点。在这项工作中,我们对 PCa 细胞进行了非靶向气相色谱-质谱(GC-MS)代谢组学分析,以证明代谢改变可能区分 PCa 细胞系与正常前列腺细胞系的概念。为此,我们评估了在两种 pH 值(pH 2 和 7)下,四种 PCa 细胞系和一种正常前列腺细胞系的细胞外介质(外代谢组)中挥发性有机化合物(VOC)谱的差异。通过 GC-MS 进行分析。多变量分析揭示了一组挥发性代谢物,可以区分癌症和正常前列腺细胞。改变最明显的代谢物包括酮、醛和有机酸。在这些代谢物中,我们重点强调了在 PCa 中与正常细胞相比明显增加的十五烷-2-酮和癸酸,以及在 PCa 细胞中明显减少的环己酮、4-甲基庚烷-2-酮、2-甲基戊烷-1,3-二醇、4-甲基苯甲醛、1-(3,5-二甲基呋喃-2-基)乙酮、苯甲酸甲酯和壬酸。PCa 的挥发性组明显受到 VOC 提取 pH 的影响,尽管判别能力相似。总的来说,我们的数据表明,VOC 监测有可能被用作 PCa 的筛查方法。