Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare).
Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare).
复制标题
DOI：
10.1007/s11306-014-0758-3
复制
发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Ulrich CM
中科院分区：
文献类型：
--
作者：
Liesenfeld DB;Habermann N;Toth R;Owen RW;Frei E;Staffa J;Schrotz-King P;Klika KD;Ulrich CM
代谢组学是筛选结直肠癌(CRC)生物标志物的重要工具。在这项研究中，我们对纳入前瞻性患者队列(ColoCare)的患者的尿代谢物进行了分析。为了描述长期临床随访中代谢组的变化，并将初始预测指标描述为可能具有预后意义的候选标志物，我们对199例结直肠癌患者术前(n=97)、术后1~8d(n=12)以及术后6个月和12个月(n=52和38)的尿样进行了GC-MS和1H-核磁共振分析。这两个数据集分别用Metover Analyst 2.0内置的单变量和多变量分析进行分析。在此基础上，构建了调整后的线性混合效应回归模型。许多来自肠道微生物组的代谢物浓度受到结直肠癌手术的影响，推测表明肿瘤诱导的细菌种类发生了变化。微生物代谢产物与疾病分期的相关性表明肠道微生物群在结直肠癌中起着重要作用。使用包含20种标志物代谢物的多变量模型(AUCROC=0.89；95%CI：0.84-0.95)，我们能够区分结直肠癌患者手术前和术后任何时间点的代谢物。据我们所知，这是第一个在前瞻性环境中跟踪研究CRC患者的代谢组学研究之一，随着时间的推移重复采样尿液。我们能够确认最初在病例对照研究中确定的标记物，以及可能作为结直肠癌预后生物标记物的候选标记物。
Metabolomics is a valuable tool for biomarker screening of colorectal cancer (CRC). In this study, we profiled the urinary metabolomes of patients enrolled in a prospective patient cohort (ColoCare). We aimed to describe changes in the metabolome in the longer clinical follow-up and describe initial predictors as candidate markers with possibly prognostic significance In total, 199 urine samples from CRC patients pre-surgery (n=97), 1–8 days post-surgery (n=12) and then after 6 and 12 months (n=52 and 38, respectively) were analyzed using both GC-MS and 1H-NMR. Both datasets were analyzed separately with built in uni- and multivariate analyses of Metaboanalyst 2.0. Furthermore, adjusted linear mixed effects regression models were constructed. Many concentrations of the metabolites derived from the gut microbiome were affected by CRC surgery, presumably indicating a tumor-induced shift in bacterial species. Associations of the microbial metabolites with disease stage indicate an important role of the gut microbiome in CRC. We were able to differentiate the metabolite profiles of CRC patients prior to surgery from those at any post-surgery timepoint using a multivariate model containing 20 marker metabolites (AUCROC=0.89; 95% CI:0.84–0.95). To the best of our knowledge, this is one of the first metabolomic studies to follow CRC patients in a prospective setting with repeated urine sampling over time. We were able to confirm markers initially identified in case-control studies and pin point metabolites which may serve as candidates for prognostic biomarkers of CRC.
登录
查看更多内容
影响因子：
37.3
作者：
Denkert C;Budczies J;Weichert W;Wohlgemuth G;Scholz M;Kind T;Niesporek S;Noske A;Buckendahl A;Dietel M;Fiehn O
通讯作者：
Fiehn O
人类结直肠癌的独特尿液代谢特征
影响因子：
4.4
作者：
Cheng, Yu;Xie, Guoxiang;Jia, Wei
通讯作者：
Jia, Wei
DOI：
10.1158/1055-9965.epi-13-0584
发表时间：
2013-12
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Liesenfeld DB;Habermann N;Owen RW;Scalbert A;Ulrich CM
通讯作者：
Ulrich CM
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.6
作者：
Aa, Jiye;Yu, Lianzhen;Wang, Guangji
通讯作者：
Wang, Guangji