Targeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring

Jiangjiang Zhu, Danijel Djukovic, Lingli Deng, Haiwei Gu, Farhan Himmati, Mohammad Abu Zaid, Elena G.abriela Chiorean, Daniel Raftery

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and a major cause of human morbidity and mortality. In addition to early detection, close monitoring of disease progression in CRC can be critical for patient prognosis and treatment decisions. Efforts have been made to develop new methods for improved early detection and patient monitoring; however, research focused on CRC surveillance for treatment response and disease recurrence using metabolomics has yet to be reported. In this proof of concept study, we applied a targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolic profiling approach focused on sequential metabolite ratio analysis of serial serum samples to monitor disease progression from 20 CRC patients. The use of serial samples reduces patient to patient metabolic variability. A partial least squares-discriminant analysis (PLS-DA) model using a panel of five metabolites (succinate, N2, N2-dimethylguanosine, adenine, citraconic acid, and 1-methylguanosine) was established, and excellent model performance (sensitivity = 0.83, specificity = 0.94, area under the receiver operator characteristic curve (AUROC) = 0.91 was obtained, which is superior to the traditional CRC monitoring marker carcinoembryonic antigen (sensitivity = 0.75, specificity = 0.76, AUROC = 0.80). Monte Carlo cross validation was applied, and the robustness of our model was clearly observed by the separation of true classification models from the random permutation models. Our results suggest the potential utility of metabolic profiling for CRC disease monitoring.

Original languageEnglish (US)
Pages (from-to)7857-7863
Number of pages7
JournalAnalytical and Bioanalytical Chemistry
Volume407
Issue number26
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Fingerprint

Metabolites
Colorectal Neoplasms
Monitoring
Serum
Disease Progression
Patient monitoring
Carcinoembryonic Antigen
Liquid chromatography
Succinic Acid
Sensitivity and Specificity
Discriminant analysis
Adenine
Metabolomics
Differentiation Antigens
Physiologic Monitoring
Discriminant Analysis
Mass spectrometry
Tandem Mass Spectrometry
Least-Squares Analysis
Liquid Chromatography

Keywords

  • Colorectal cancer
  • Disease progression monitoring
  • Metabolomics
  • Sequential metabolite ratio analysis
  • Serial patient samples
  • Serum metabolites
  • Targeted metabolic profiling

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

Cite this

Targeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring. / Zhu, Jiangjiang; Djukovic, Danijel; Deng, Lingli; Gu, Haiwei; Himmati, Farhan; Abu Zaid, Mohammad; Chiorean, Elena G.abriela; Raftery, Daniel.

In: Analytical and Bioanalytical Chemistry, Vol. 407, No. 26, 01.10.2015, p. 7857-7863.

Research output: Contribution to journalArticle

Zhu, Jiangjiang ; Djukovic, Danijel ; Deng, Lingli ; Gu, Haiwei ; Himmati, Farhan ; Abu Zaid, Mohammad ; Chiorean, Elena G.abriela ; Raftery, Daniel. / Targeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring. In: Analytical and Bioanalytical Chemistry. 2015 ; Vol. 407, No. 26. pp. 7857-7863.
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