Human plasma metabolomics for identifying differential metabolites and predicting molecular subtypes of breast cancer

Oncotarget. 2016 Mar 1;7(9):9925-38. doi: 10.18632/oncotarget.7155.

Abstract

Purpose: This work aims to identify differential metabolites and predicting molecular subtypes of breast cancer (BC).

Methods: Plasma samples were collected from 96 BC patients and 79 normal participants. Metabolic profiles were determined by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry based on multivariate statistical data analysis.

Results: We observed 64 differential metabolites between BC and normal group. Compared to human epidermal growth factor receptor 2 (HER2)-negative patients, HER2-positive group showed elevated aerobic glycolysis, gluconeogenesis, and increased fatty acid biosynthesis with reduced Krebs cycle. Compared with estrogen receptor (ER)-negative group, ER-positive patients showed elevated alanine, aspartate and glutamate metabolism, decreased glycerolipid catabolism, and enhanced purine metabolism. A panel of 8 differential metabolites, including carnitine, lysophosphatidylcholine (20:4), proline, alanine, lysophosphatidylcholine (16:1), glycochenodeoxycholic acid, valine, and 2-octenedioic acid, was identified for the classification of BC subtypes. These markers showed potential diagnostic value with average area under the curve at 0.925 (95% CI 0.867-0.983) for the training set (n=51) and 0.893 (95% CI 0.847-0.939) for the test set (n=45).

Conclusion: Human plasma metabolomics is useful in identifying differential metabolites and predicting breast cancer subtypes.

Keywords: breast cancer; differential metabolites; human plasma metabolomics; molecular subtypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / blood*
  • Breast Neoplasms / classification
  • Breast Neoplasms / metabolism
  • Chromatography, Liquid
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Mass Spectrometry
  • Metabolome*
  • Metabolomics / methods*
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2