engleski

Metabolic alterations in breast cancer: searching for circulating makers of breast cancer risk

Breast cancer (BC) is a heterogeneous disease and one of the major causes of cancer death in women. One of the main hallmarks of cancer is the ability of cancer cells to alter their metabolic phenotype, which allows them to survive and proliferate against all odds. Therefore, the aim of this study was to apply untargeted metabolomics approach (LC-MS) in order to identify new molecular targets associated with BC pathology. Study included plasma samples from BC patients (N=41) and matching female controls (N=30). After appropriate multivariate and univariate statistical analysis, a total of 57 chemical compounds (detected by LC-MS positive or negative ionization mode) were found to be significantly altered in BC patients. The resulting list of statistically significant accurate masses was annotated using the CEU Mass Mediator search tool (http://ceumass.eps.uspceu.es/mediator/), and the biological role of each suggested compound was additionally evaluated to exclude the impossible identification matches. Our results indicate a significant increase in the expression of different fatty acyls, including several straight chain, branched and unsaturated fatty acids, docosanoids, eicosanoids, octadecanoids, fatty aldehydes and amides. Increased levels of certain monoacylglycerols and different glycerophospholipids (glycerophosphates and glycerophosphocholines) were also found to be characteristic for BC subjects. We also detected alteration of amino acid and bilirubin metabolism in BC patients and differential expression of C19 and C20 steroids. These findings suggest a key role of lipid classes and molecular species in BC growth and development and possibly lead us a step closer to new metabolic targets in BC treatment.

breast cancer ; metabolomics ; plasma ; untargeted approach

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