Early detection of recurrent breast cancer using metabolite profiling.
We report on the development of a monitoring test for recurrent breast cancer, using metabolite-profiling methods. Using a combination of nuclear magnetic resonance (NMR) and two-dimensional gas chromatography-mass spectrometry (GC×GC-MS) methods, we analyzed the metabolite profiles of 257 retrospective serial serum samples from 56 previously diagnosed and surgically treated breast cancer patients. One hundred sixteen of the serial samples were from 20 patients with recurrent breast cancer, and 141 samples were from 36 patients with no clinical evidence of the disease during ∼6 years of sample collection. NMR and GC×GC-MS data were analyzed by multivariate statistical methods to compare identified metabolite signals between the recurrence samples and those with no evidence of disease. Eleven metabolite markers (seven from NMR and four from GC×GC-MS) were shortlisted from an analysis of all patient samples by using logistic regression and 5-fold cross-validation. A partial least squares discriminant analysis model built using these markers with leave-one-out cross-validation provided a sensitivity of 86% and a specificity of 84% (area under the receiver operating characteristic curve = 0.88). Strikingly, 55% of the patients could be correctly predicted to have recurrence 13 months (on average) before the recurrence was clinically diagnosed, representing a large improvement over the current breast cancer-monitoring assay CA 27.29. To the best of our knowledge, this is the first study to develop and prevalidate a prediction model for early detection of recurrent breast cancer based on metabolic profiles. In particular, the combination of two advanced analytical methods, NMR and MS, provides a powerful approach for the early detection of recurrent breast cancer.
Department of Chemistry, Purdue University, Matrix-Bio, Inc, West Lafayette, Indiana 47907, USA.
Vincent M
VM
Asiago
Leiddy Z
LZ
Alvarado
Narasimhamurthy
N
Shanaiah
G A Nagana
GA
Gowda
Kwadwo
K
Owusu-Sarfo
Robert A
RA
Ballas
Daniel
D
Raftery
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis*; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015996:Survival Rate
D014408:Biomarkers, Tumor; D012333:RNA, Messenger