Leichtle Alexander Benedikt, Nuoffer Jean-Marc, Ceglarek Uta, Kase Julia, Conrad Tim, Witzigmann Helmut, Thiery Joachim, Fiedler Georg Martin
Metabolomics. 2012 Aug;8(4):643-653. doi: 10.1007/s11306-011-0357-5. Epub 2011 Sep 16.
Mass spectrometry-based serum metabolic profiling is a promising tool to analyse complex cancer associated metabolic alterations, which may broaden our pathophysiological understanding of the disease and may function as a source of new cancer-associated biomarkers. Highly standardized serum samples of patients suffering from colon cancer (n = 59) and controls (n = 58) were collected at the University Hospital Leipzig. We based our investigations on amino acid screening profiles using electrospray tandem-mass spectrometry. Metabolic profiles were evaluated using the Analyst 1.4.2 software. General, comparative and equivalence statistics were performed by R 2.12.2. 11 out of 26 serum amino acid concentrations were significantly different between colorectal cancer patients and healthy controls. We found a model including CEA, glycine, and tyrosine as best discriminating and superior to CEA alone with an AUROC of 0.878 (95% CI 0.815-0.941). Our serum metabolic profiling in colon cancer revealed multiple significant disease-associated alterations in the amino acid profile with promising diagnostic power. Further large-scale studies are necessary to elucidate the potential of our model also to discriminate between cancer and potential differential diagnoses. In conclusion, serum glycine and tyrosine in combination with CEA are superior to CEA for the discrimination between colorectal cancer patients and controls.
基于质谱的血清代谢谱分析是一种很有前景的工具,可用于分析与癌症相关的复杂代谢改变,这可能会拓宽我们对该疾病病理生理学的理解,并可能成为新的癌症相关生物标志物的来源。在莱比锡大学医院收集了结肠癌患者(n = 59)和对照组(n = 58)的高度标准化血清样本。我们基于使用电喷雾串联质谱的氨基酸筛选谱进行研究。使用Analyst 1.4.2软件评估代谢谱。使用R 2.12.2进行一般、比较和等效性统计。在结直肠癌患者和健康对照之间,26种血清氨基酸浓度中的11种存在显著差异。我们发现一个包含癌胚抗原(CEA)、甘氨酸和酪氨酸的模型具有最佳鉴别能力,且优于单独使用CEA,其受试者工作特征曲线下面积(AUROC)为0.878(95%置信区间0.815 - 0.941)。我们对结肠癌的血清代谢谱分析揭示了氨基酸谱中多个与疾病相关的显著改变,具有可观的诊断能力。需要进一步的大规模研究来阐明我们的模型在区分癌症和潜在鉴别诊断方面的潜力。总之,血清甘氨酸和酪氨酸与CEA联合使用在区分结直肠癌患者和对照组方面优于单独使用CEA。