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晚期腺瘤和结直肠癌患者粪便样本的综合代谢组学分析

A Comprehensive Metabolomics Analysis of Fecal Samples from Advanced Adenoma and Colorectal Cancer Patients.

作者信息

Telleria Oiana, Alboniga Oihane E, Clos-Garcia Marc, Nafría-Jimenez Beatriz, Cubiella Joaquin, Bujanda Luis, Falcón-Pérez Juan Manuel

机构信息

Exosomes Laboratory, CIC bioGUNE-BRTA, CIBERehd, Bizkaia Technology Park, 48160 Bilbao, Spain.

Metabolomics Platform, CIC bioGUNE-BRTA, CIBERehd, Bizkaia Technology Park, 48160 Bilbao, Spain.

出版信息

Metabolites. 2022 Jun 15;12(6):550. doi: 10.3390/metabo12060550.

Abstract

Accurate diagnosis of colorectal cancer (CRC) still relies on invasive colonoscopy. Noninvasive methods are less sensitive in detecting the disease, particularly in the early stage. In the current work, a metabolomics analysis of fecal samples was carried out by ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS). A total of 1380 metabolites were analyzed in a cohort of 120 fecal samples from patients with normal colonoscopy, advanced adenoma (AA) and CRC. Multivariate analysis revealed that metabolic profiles of CRC and AA patients were similar and could be clearly separated from control individuals. Among the 25 significant metabolites, sphingomyelins (SM), lactosylceramides (LacCer), secondary bile acids, polypeptides, formiminoglutamate, heme and cytidine-containing pyrimidines were found to be dysregulated in CRC patients. Supervised random forest (RF) and logistic regression algorithms were employed to build a CRC accurate predicted model consisting of the combination of hemoglobin (Hgb) and bilirubin E,E, lactosyl-N-palmitoyl-sphingosine, glycocholenate sulfate and STLVT with an accuracy, sensitivity and specificity of 91.67% (95% Confidence Interval (CI) 0.7753-0.9825), 0.7 and 1, respectively.

摘要

结直肠癌(CRC)的准确诊断仍依赖于侵入性结肠镜检查。非侵入性方法在检测该疾病时敏感性较低,尤其是在早期阶段。在当前的研究中,通过超高效液相色谱 - 串联质谱(UPLC-MS/MS)对粪便样本进行了代谢组学分析。在一组来自结肠镜检查正常、患有高级别腺瘤(AA)和CRC的患者的120份粪便样本中,共分析了1380种代谢物。多变量分析显示,CRC和AA患者的代谢谱相似,并且可以与对照个体明显区分开来。在25种显著的代谢物中,发现鞘磷脂(SM)、乳糖神经酰胺(LacCer)、次级胆汁酸、多肽、亚胺甲基谷氨酸、血红素和含胞嘧啶的嘧啶在CRC患者中失调。采用监督随机森林(RF)和逻辑回归算法构建了一个CRC准确预测模型,该模型由血红蛋白(Hgb)和胆红素E、E、乳糖 - N - 棕榈酰 - 鞘氨醇、硫酸甘氨胆酸盐和STLVT组合而成,其准确率、敏感性和特异性分别为91.67%(95%置信区间(CI)0.7753 - 0.9825)、0.7和1。

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