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

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

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

Table1_Clethra fimbriata hexanic extract triggers alteration in the energy metabolism in epimastigotes of Trypanosoma cruzi.DOCX

Chagas disease (ChD), caused by Trypanosoma cruzi, is endemic in American countries and an estimated 8 million people worldwide are chronically infected. Currently, only two drugs are available for therapeutic use against T. cruzi and their use is controversial due to several disadvantages associated with side effects and low compliance with treatment. Therefore, there is a need to search for new tripanocidal agents. Natural products have been considered a potential innovative source of effective and selective agents for drug development to treat T. cruzi infection. Recently, our research group showed that hexanic extract from Clethra fimbriata (CFHEX) exhibits anti-parasitic activity against all stages of T. cruzi parasite, being apoptosis the main cell death mechanism in both epimastigotes and trypomastigotes stages. With the aim of deepening the understanding of the mechanisms of death induced by CFHEX, the metabolic alterations elicited after treatment using a multiplatform metabolomics analysis (RP/HILIC-LC-QTOF-MS and GC-QTOF-MS) were performed. A total of 154 altered compounds were found significant in the treated parasites corresponding to amino acids (Arginine, threonine, cysteine, methionine, glycine, valine, proline, isoleucine, alanine, leucine, glutamic acid, and serine), fatty acids (stearic acid), glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine), sulfur compounds (trypanothione) and carboxylic acids (pyruvate and phosphoenolpyruvate). The most affected metabolic pathways were mainly related to energy metabolism, which was found to be decrease during the evaluated treatment time. Further, exogenous compounds of the triterpene type (betulinic, ursolic and pomolic acid) previously described in C. fimbriata were found inside the treated parasites. Our findings suggest that triterpene-type compounds may contribute to the activity of CFHEX by altering essential processes in the parasite.</p