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

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.

Predicting dynamic response to neoadjuvant chemotherapy in breast cancer: a novel metabolomics approach

“…Specifically postsurgery, a significant decrease in Trp plasmatic concentrations was observed, as previously reported in serum and plasma of BC patients [58][59][60]. In this regard, Trp catabolism dysregulation is known to indirectly contribute to cancer progression by the kynurenine (Kyn) pathway [61][62][63], although no associations with response or sensitivity to chemotherapy were observed in previous studies, which coincides with our observations [22,64]. In this line, further investigating the metabolome alteration related to treatment response is still needed to better understand the behavior of the LB and HER2+ molecular subtypes in response to NACT.…”

Metabolomic Analysis of Plasma from Breast Tumour Patients. A Pilot Study

“…Metabolomics represents a powerful tool for the extraction of features about the health status of patients with a suspect of breast tumour. As reported in recent publications about metabolomics and cancer, 7 , 8 , 19 , 21 a fingerprint with the capability to improve specificity and sensibility of the radiological classification of tumours can be extracted from the peripherical plasma or specific tissue. BI-RADS classification can be enhanced by the quantification of the metabolites list from Metabolomics analysis.…”

Gold‐Doped Covalent Organic Framework Reveals Specific Serum Metabolic Fingerprints as Point of Crohn's Disease Diagnosis

“…Mass spectrometry (MS) technology features by the characteristics of high sensitivity, high throughput, and high‐speed analysis, metabolomics based on which has been widely used in the study of metabolic pathway, [ 7 ] disease diagnose [ 8 ] and classification, [ 9 ] as well as biomarker screening. [ 8a,9,10 ] Especially, laser desorption/ionization mass spectrometry (LDI‐MS) has been demonstrated to be an excellent choice in revealing the humoral characteristic fingerprinting owing to its detection speed at the millisecond level and sample dosage at nanoliter or microliter level. [ 11 ] Moreover, nanomaterials have excellent optical properties, homogeneous sample distribution, and large surface areas.…”