Global and targeted serum metabolic profiling of colorectal cancer progression

Yin Long, Beatriz Sanchez-Espiridion, Moubin Lin, Lindsey White, Lopa Mishra, Gottumakkala S. Raju, Scott Kopetz, Cathy Eng, Michelle A.T. Hildebrandt, David W. Chang, Yuanqing Ye, Dong Liang, Xifeng Wu

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

BACKGROUND: Patients with colorectal adenoma polyps (PLPs) are at higher risk for developing colorectal cancer (CRC). However, the development of improved and robust biomarkers to enable the screening, surveillance, and early detection of PLPs and CRC continues to be a challenge. The aim of this study was to identify biomarkers of progression to CRC through metabolomic profiling of human serum samples with a multistage approach. METHODS: Metabolomic profiling was conducted with the Metabolon platform for 30 CRC patients, 30 PLP patients, and 30 control subjects, and this was followed by the targeted validation of the top metabolites in an additional set of 50 CRC patients, 50 PLP patients, and 50 controls with liquid chromatography–tandem mass spectrometry. Unconditional multivariate logistic regression models, adjusted for covariates, were used to evaluate associations with PLP and CRC risk. RESULTS: For the discovery phase, 404 serum metabolites were detected, with 50 metabolites showing differential levels between CRC patients, PLP patients, and controls (P for trend <.05). After validation, the 3 top metabolites (xanthine, hypoxanthine, and d-mannose) were validated: lower levels of xanthine and hypoxanthine and higher levels of d-mannose were found in PLP and CRC cases versus controls. A further exploratory analysis of metabolic pathways revealed key roles for the urea cycle and caffeine metabolism associated with PLP and CRC risk. In addition, a joint effect of the top metabolites with smoking and a significant interaction with the body mass index were observed. An analysis of the ratio of hypoxanthine levels to xanthine levels indicated an association with CRC progression. CONCLUSIONS: These results suggest the potential utility of circulating metabolites as novel biomarkers for the early detection of CRC. Cancer 2017;123:4066-74.

Original languageEnglish (US)
Pages (from-to)4066-4074
Number of pages9
JournalCancer
Volume123
Issue number20
DOIs
StatePublished - Oct 15 2017

Keywords

  • adenoma polyps
  • colorectal cancer
  • d-mannose
  • metabolomic profiling
  • xanthine/hypoxanthine ratio

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Global and targeted serum metabolic profiling of colorectal cancer progression'. Together they form a unique fingerprint.

Cite this