RESUMO
Sphingolipids are structurally diverse and their metabolic pathways highly complex, which makes it difficult to follow all of the subspecies in a biological system, even using "lipidomic" approaches. This report describes a method to use transcriptomic data to visualize and predict potential differences in sphingolipid composition, and it illustrates its use with published data for cancer cell lines and tumors. In addition, several novel sphingolipids that were predicted to differ between MDA-MB-231 and MCF7 cells based on published microarray data for these breast cancer cell lines were confirmed by mass spectrometry. For the data that we were able to find for these comparisons, there was a significant match between the gene expression data and sphingolipid composition (P < 0.001 by Fisher's exact test). Upon considering the large number of gene expression datasets produced in recent years, this simple integration of two types of "omic" technologies ("transcriptomics" to direct "sphingolipidomics") might facilitate the discovery of useful relationships between sphingolipid metabolism and disease, such as the identification of new biomarkers.
Assuntos
Adenocarcinoma Papilar , Neoplasias da Mama/metabolismo , Carcinoma Ductal , Proteômica/métodos , Esfingolipídeos/genética , Algoritmos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Metabolismo dos Lipídeos , Espectrometria de Massas , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Mensageiro/análise , RNA Mensageiro/isolamento & purificação , Esfingolipídeos/análise , Esfingolipídeos/química , Esfingolipídeos/metabolismoRESUMO
The sphingolipidome is the portion of the lipidome that encompasses all sphingoid bases and their derivatives. Whereas the most studied sphingoid base is sphingosine [(2S,3R,4E)-2-aminooctadecene-1,3-diol], mammals have dozens of structural variants, and hundreds of additional types have been found in other eukaryotic organisms and some bacteria and viruses. Multiplying these figures by the N-acyl-derivatives ("ceramides") and the more than 500 phospho- and glyco- headgroups places the number of discrete molecular species in the tens of thousands or higher. Structure-specific, quantitative information about a growing fraction of the sphingolipidome can now be obtained using various types of chromatography coupled with tandem mass spectrometry, and application of these methods is producing many surprises regarding sphingolipid structure, metabolism, and function. Such large data sets can be difficult to interpret, but the development of tools that display results from genomic and lipidomic studies in a pathway relational, nodal, context can make it easier for investigators to deal with this complexity.
