Multiplatform plasma metabolic and lipid fingerprinting of breast cancer: A pilot control-case study in Colombian Hispanic women

<div><p>Breast cancer (BC) is a highly heterogeneous disease associated with metabolic reprogramming. The shifts in the metabolome caused by BC still lack data from Latin populations of Hispanic origin. In this pilot study, metabolomic and lipidomic approaches were performed to establish a plasma metabolic fingerprint of Colombian Hispanic women with BC. Data from ¹H-NMR, GC-MS and LC-MS were combined and compared. Statistics showed discrimination between breast cancer and healthy subjects on all analytical platforms. The differentiating metabolites were involved in glycerolipid, glycerophospholipid, amino acid and fatty acid metabolism. This study demonstrates the usefulness of multiplatform approaches in metabolic/lipid fingerprinting studies to broaden the outlook of possible shifts in metabolism. Our findings propose relevant plasma metabolites that could contribute to a better understanding of underlying metabolic shifts driven by BC in women of Colombian Hispanic origin. Particularly, the understanding of the up-regulation of long chain fatty acyl carnitines and the down-regulation of cyclic phosphatidic acid (cPA). In addition, the mapped metabolic signatures in breast cancer were similar but not identical to those reported for non-Hispanic women, despite racial differences.</p></div

Venn diagram.

<p>Venn diagram for the number of differentiating metabolites in BCP group identified in each chromatographic technique coupled to mass spectrometry (blue circle: MF/GC-MS, yellow circle: MF/LC-MS(±), green circle: LF/LC-MS(±).</p

Compounds with statistical significance identified by lipid fingerprinting using LC-MS(±).

<p>Compounds with statistical significance identified by lipid fingerprinting using LC-MS(±).</p

Pathway analysis.

<p>Pathway analysis displaying metabolic pathways arranged by scores from pathway enrichment (y axis) and from topology analysis (x axis) using MetaboAnalyst 3.0 tool. The color and size of each circle is based on <i>p</i>-values and pathway impact values, respectively [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190958#pone.0190958.ref057" target="_blank">57</a>].</p

Characteristics of studied subjects.

<p>Characteristics of studied subjects.</p

Chemical shifts of compounds with statistical significance identified by ¹H-NMR.

<p>Chemical shifts of compounds with statistical significance identified by ¹H-NMR.</p

Compounds with statistical significance identified by GC-MS.

<p>Compounds with statistical significance identified by GC-MS.</p

Compounds with statistical significance identified by metabolic fingerprinting using LC-MS(±).

<p>Compounds with statistical significance identified by metabolic fingerprinting using LC-MS(±).</p

Validation results of PPD in human urine.

<p>Inter- and intraday accuracy and precision measurements (<i>n = 3</i> for each value). The mean relative error of each concentration is expressed as % bias and the reproducibility is depicted as the coefficient of variation (% CV). Intraday accuracy and precision were also determined on the HPLC-UV system.</p

Validation results of PPD in human urine.

<p>MALDI-MS/MS assay: linearity, lower limit of quantification (LLOQ), recovery (at 130, 400 and 800 µmol/L) and stability after addition of formic acid.</p