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采用 1H HR MAS MR 波谱和化学计量分析对微卫星不稳定型结肠癌患者的鉴别。

Discrimination of patients with microsatellite instability colon cancer using 1H HR MAS MR spectroscopy and chemometric analysis.

机构信息

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

出版信息

J Proteome Res. 2010 Jul 2;9(7):3664-70. doi: 10.1021/pr100176g.

Abstract

The primary aim of this study was to analyze human colon cancer and normal adjacent tissue using (1)H HR MAS MR spectroscopy and chemometric analyses, evaluating possible biomarkers for colon cancer. The secondary aim was to investigate metabolic profiles of tissue samples (n = 63, 31 patients) with microsatellite instability (MSI-H) compared to microsatellite stable (MSS) colon tissue. Our hypothesis was that this method may provide an alternative to MSI genotyping. Cancer samples were clearly separated from normal adjacent mucosa by 100% accuracy. Several metabolites such as lactate, taurine, glycine, myo-inositol, scyllo-inositol, phosphocholine (PC), glycerophosphocholine (GPC), creatine, and glucose were identified as potential biomarkers for cancer detection. Adenomas (n = 4) were also separated from cancer and normal samples mainly based on higher GPC and PC levels. Interestingly, metabolic differences in normal colon mucosa between MSI-H and MSS patients were observed. MSI status was validated with 80% accuracy with a sensitivity and specificity of 79% and 82%, respectively, including both cancer and normal samples The metabolic differences between MSI-H and MSS may be very interesting in the early detection of cancer development and of high clinical importance in the work of improving diagnosis and characterization of colon cancer.

摘要

本研究的主要目的是使用(1)H HR MAS MR 光谱和化学计量学分析方法分析人结肠癌和正常相邻组织,评估结肠癌的可能生物标志物。次要目的是研究微卫星不稳定(MSI-H)与微卫星稳定(MSS)结肠癌组织相比组织样本(n = 63,31 例患者)的代谢谱。我们的假设是,这种方法可能提供一种替代 MSI 基因分型的方法。癌症样本与正常相邻粘膜的准确率为 100%。鉴定出几种代谢物,如乳酸盐、牛磺酸、甘氨酸、肌醇、海鞘素、磷酸胆碱(PC)、甘油磷酸胆碱(GPC)、肌酸和葡萄糖,它们可能是癌症检测的生物标志物。腺瘤(n = 4)也主要基于更高的 GPC 和 PC 水平与癌症和正常样本分离。有趣的是,在 MSI-H 和 MSS 患者的正常结肠粘膜之间观察到代谢差异。MSI 状态的验证准确率为 80%,灵敏度和特异性分别为 79%和 82%,包括癌症和正常样本。MSI-H 和 MSS 之间的代谢差异在癌症发展的早期检测中可能非常有趣,并且在改善结肠癌的诊断和特征描述方面具有重要的临床意义。

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