Plasma metabolites as possible biomarkers for diagnosis of breast cancer

• Published in: PloS one 2019-12, Vol.14 (12), p.e0225129-e0225129
• Main Authors: Park, Jiwon, Shin, Yumi, Kim, Tae Hyun, Kim, Dong-Hyun, Lee, Anbok
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - blood; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - diagnosis; Cancer diagnosis; Cancer patients; Cancer research; Carnitine - analogs & derivatives; Carnitine - blood; Case-Control Studies; Cell growth; Chromatography; Chromatography, Liquid; Criminal investigation; Diagnosis; Diagnostic systems; Disease; Docosahexaenoic acid; Docosahexaenoic Acids - blood; EDTA; Fatty acids; Female; Hormones; Hospitals; Humans; Hypoxanthine; Hypoxanthine - blood; Liquid chromatography; Mammography; Mass Spectrometry; Mass spectroscopy; Medical diagnosis; Medical prognosis; Medical schools; Medical screening; Medicine; Medicine and Health Sciences; Metabolism; Metabolites; Metabolomics; Middle Aged; NMR; Nuclear magnetic resonance; Omega 3 fatty acids; Phase transitions; Profiling; Prostate cancer; Purines; Pyrrolidonecarboxylic Acid - blood; Quantitative analysis; Research and analysis methods; Scientific imaging; Spectroscopy; Surgery; Tumors; Ultrasonic imaging; Unsaturated fatty acids
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0225129

Metabolomic approaches have been used to identify new diagnostic biomarkers for various types of cancers, including breast cancer. In this study, we aimed to identify potential biomarkers of breast cancer using plasma metabolic profiling. Furthermore, we analyzed whether these biomarkers had relationships with clinicopathological characteristics of breast cancer. Our study used two liquid chromatography-mass spectrometry sets: a discovery set (40 breast cancer patients and 30 healthy controls) and a validation set (30 breast cancer patients and 16 healthy controls). All breast cancer patients were randomly selected from among stage I-III patients who underwent surgery between 2011 and 2016. First, metabolites distinguishing cancer patients from healthy controls were identified in the discovery set. Then, consistent and reproducible metabolites were evaluated in terms of their utility as possible biomarkers of breast cancer. Receiver operating characteristic (ROC) analysis was applied to the discovery set, and ROC cut-off values for the identified metabolites derived therein were applied to the validation set to determine their diagnostic performance. Ultimately, four candidate biomarkers (L-octanoylcarnitine, 5-oxoproline, hypoxanthine, and docosahexaenoic acid) were identified. L-octanoylcarnitine showed the best diagnostic performance, with a 100.0% positive predictive value. Also, L-octanoylcarnitine levels differed according to tumor size and hormone receptor expression. The plasma metabolites identified in this study show potential as biomarkers allowing early diagnosis of breast cancer. However, the diagnostic performance of the metabolites needs to be confirmed in further studies with larger sample sizes.