A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics.
A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics.
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DOI：
10.1038/bjc.2016.243
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发表时间：
2016-09-27
影响因子：
8.8
通讯作者：
Bathe, Oliver F.
中科院分区：
文献类型：
--
作者：
Farshidfar, Farshad;Weljie, Aalim M.;Kopciuk, Karen A.;Hilsden, Robert;McGregor, S. Elizabeth;Buie, W. Donald;MacLean, Anthony;Vogel, Hans J.;Bathe, Oliver F.
结直肠癌（CRC）的及时诊断和分类受到不满意的临床检测的阻碍。我们的目的是使用单一检测构建一个基于血液的生物标志物系列，适用于CRC检测，鉴定和分期。采用气相色谱-质谱联用技术（GC-MS）分析31例腺瘤患者、320例不同分期结直肠癌患者和254例健康对照者的血清代谢物组学特征。通过正交偏最小二乘判别分析（OPLS-DA）的训练集上的CRC的诊断模型，然后验证一个独立的数据集。产生了适合于鉴定腺瘤、预后不良的II期CRC和区分不同阶段的代谢组学模型。构建了具有显著多变量性能（R2 Y =0.46，Q2 Y =0.39）的CRC诊断特征，然后进行验证（灵敏度85%特异性86%）。受试者工作特征曲线下面积为0.91（95% CI，0.87-0.96）。还可检测到腺瘤（R2 Y =0.35，Q2 Y =0.26，内部AUROC=0.81，95%CI，0.70-0.92）。同样特别感兴趣的是，我们确定了模型，分层阶段II的预后，并按阶段分类的情况下。使用单一检测系统，一套基于循环代谢物的CRC生物标志物能够实现早期检测，预测和初步分期信息。需要进行基于人群的外部研究来评估我们发现的可重复性，并评估这些生物标志物的临床益处。
Timely diagnosis and classification of colorectal cancer (CRC) are hindered by unsatisfactory clinical assays. Our aim was to construct a blood-based biomarker series using a single assay, suitable for CRC detection, prognostication and staging. Serum metabolomic profiles of adenoma (N=31), various stages of CRC (N=320) and healthy matched controls (N=254) were analysed by gas chromatography-mass spectrometry (GC-MS). A diagnostic model for CRC was derived by orthogonal partial least squares-discriminant analysis (OPLS-DA) on a training set, and then validated on an independent data set. Metabolomic models suitable for identifying adenoma, poor prognosis stage II CRC and discriminating various stages were generated. A diagnostic signature for CRC with remarkable multivariate performance (R2Y=0.46, Q2Y=0.39) was constructed, and then validated (sensitivity 85% specificity 86%). Area under the receiver-operating characteristic curve was 0.91 (95% CI, 0.87–0.96). Adenomas were also detectable (R2Y=0.35, Q2Y=0.26, internal AUROC=0.81, 95% CI, 0.70–0.92). Also of particular interest, we identified models that stratified stage II by prognosis, and classified cases by stage. Using a single assay system, a suite of CRC biomarkers based on circulating metabolites enables early detection, prognostication and preliminary staging information. External population-based studies are required to evaluate the repeatability of our findings and to assess the clinical benefits of these biomarkers.
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影响因子：
3.5
作者：
Bathe OF;Farshidfar F
通讯作者：
Farshidfar F
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
8.8
作者：
Croner, R. S.;Geppert, C-I;Zuber, M.
通讯作者：
Zuber, M.
影响因子：
3.7
作者：
Nishiumi S;Kobayashi T;Ikeda A;Yoshie T;Kibi M;Izumi Y;Okuno T;Hayashi N;Kawano S;Takenawa T;Azuma T;Yoshida M
通讯作者：
Yoshida M
影响因子：
15.8
作者：
Heitman SJ;Hilsden RJ;Au F;Dowden S;Manns BJ
通讯作者：
Manns BJ