Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer

SIMPLE SUMMARY: Breast cancer is the leading cause of female cancer-related deaths worldwide. New technologies with enhanced sensitivity and specificity for early diagnosis and tailored monitoring are in critical demand. Thus, metabolomics appears to be a growing tool in order to detect molecular differences between distinct groups. In this case, an untargeted analytical approach was used to identify metabolomics differences between molecular subtypes of breast cancer in comparison with healthy matched controls. Footprints for each breast cancer subtype provided diagnostic capacities with an area under the receiver-operating characteristic curve above 0.85, which suggests that our results may represent a major advance towards the improvement of personalized medicine and precise targeted therapies for the various breast cancer phenotypes. To validate these molecular profiling as potential therapeutic strategies for the different breast cancer subtypes, further analysis and larger cohorts would be necessary in the near future. ABSTRACT: Purpose: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. Methods: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. Results: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected p-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. Conclusion: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.