title: Human plasma metabolomics for identifying differential metabolites and predicting molecular subtypes of breast cancer.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Human plasma metabolomics is useful in identifying differential metabolites and predicting breast cancer subtypes.
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Yong
authors: Y
authors: Fan
authors: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Xin
authors: X
authors: Zhou
authors: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Tian-Song
authors: TS
authors: Xia
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Zhuo
authors: Z
authors: Chen
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Jin
authors: J
authors: Li
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Qun
authors: Q
authors: Liu
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Raphael N
authors: RN
authors: Alolga
authors: Emergency Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Yan
authors: Y
authors: Chen
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Mao-De
authors: MD
authors: Lai
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Ping
authors: P
authors: Li
authors: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Wei
authors: W
authors: Zhu
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors: Lian-Wen
authors: LW
authors: Qi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000145:classification / Q000378:metabolism; D002853:Chromatography, Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
keywords: breast cancer; differential metabolites; human plasma metabolomics; molecular subtypes