Distinct urinary metabolic profile of human colorectal cancer

Yu Cheng, Guoxiang Xie, Tianlu Chen, Yunping Qiu, Xia Zou, Minhua Zheng, Binbin Tan, Bo Feng, Taotao Dong, Pingang He, Linjing Zhao, Aihua Zhao, Lisa X. Xu, Yan Zhang, Wei Jia

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

A full spectrum of metabolic aberrations that are directly linked to colorectal cancer (CRC) at early curable stages is critical for developing and deploying molecular diagnostic and therapeutic approaches that will significantly improve patient survival. We have recently reported a urinary metabonomic profiling study on CRC subjects (n = 60) and health controls (n = 63), in which a panel of urinary metabolite markers was identified. Here, we report a second urinary metabonomic study on a larger cohort of CRC (n = 101) and healthy subjects (n = 103), using gas chromatography time-of-flight mass spectrometry and ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry. Consistent with our previous findings, we observed a number of dysregulated metabolic pathways, such as glycolysis, TCA cycle, urea cycle, pyrimidine metabolism, tryptophan metabolism, polyamine metabolism, as well as gut microbial-host co-metabolism in CRC subjects. Our findings confirm distinct urinary metabolic footprints of CRC patients characterized by altered levels of metabolites derived from gut microbial-host co-metabolism. A panel of metabolite markers composed of citrate, hippurate, p-cresol, 2-aminobutyrate, myristate, putrescine, and kynurenate was selected, which was able to discriminate CRC subjects from their healthy counterparts. A receiver operating characteristic curve (ROC) analysis of these markers resulted in an area under the receiver operating characteristic curve (AUC) of 0.993 and 0.998 for the training set and the testing set, respectively. These potential metabolite markers provide a novel and promising molecular diagnostic approach for the early detection of CRC.

Original languageEnglish (US)
Pages (from-to)1354-1363
Number of pages10
JournalJournal of Proteome Research
Volume11
Issue number2
DOIs
StatePublished - Feb 3 2012
Externally publishedYes

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Keywords

  • colorectal cancer
  • gas chromatography time-of-flight mass spectrometry
  • metabolic profiling
  • metabonomics
  • ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry
  • urine

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Cheng, Y., Xie, G., Chen, T., Qiu, Y., Zou, X., Zheng, M., Tan, B., Feng, B., Dong, T., He, P., Zhao, L., Zhao, A., Xu, L. X., Zhang, Y., & Jia, W. (2012). Distinct urinary metabolic profile of human colorectal cancer. Journal of Proteome Research, 11(2), 1354-1363. https://doi.org/10.1021/pr201001a