Abstract
BackgroundTriple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Furthermore, detailed biological information about the disease is lacking. This study investigated characteristics of metabolic pathways in TN.MethodsWe performed the metabolome analysis of 74 breast cancer tissues and the corresponding normal breast tissues using LC/MS. Furthermore, we classified the breast cancer tissues into ER-positive, PgR-positive, HER2-negative breast cancer (EP+H-) and TN, and then the differences in their metabolic pathways were investigated. The RT-PCR and immunostaining were carried out to examine the expression of ELOVL1, 2, 3, 4, 5, 6, and 7.ResultsWe identified 142 of hydrophilic metabolites and 278 of hydrophobic lipid metabolites in breast tissues. We found the differences between breast cancer and normal breast tissues in choline metabolism, glutamine metabolism, lipid metabolism, and so on. Most characteristic of comparison between EP+H- and TN were differences in fatty acid metabolism was which were related to the elongation of very long chain fatty acids were detected between TN and EP+H-. Real-time RT-PCR showed that the mRNA expression levels of ELOVL1, 5, and 6 were significantly upregulated by 8.5-, 4.6- and 7.0-fold, respectively, in the TN tumors compared with their levels in the corresponding normal breast tissue samples. Similarly, the mRNA expression levels of ELOVL1, 5, and 6 were also significantly higher in the EP+H- tissues than in the corresponding normal breast tissues (by 4.9-, 3.4-, and 2.1-fold, respectively). The mRNA expression level of ELOVL6 was 2.6-fold higher in the TN tumors than in the EP+H- tumors. During immunostaining, the TN and EP+H- tumors demonstrated stronger ELOVL1 and 6 staining than the corresponding normal breast tissues, but ELOVL5 was not stained strongly in the TN or EP+H- tumors. Furthermore, the TN tumors exhibited stronger ELOVL1 and 6 staining than the EP+H- tumors.ConclusionsMarked differences in fatty acid metabolism pathways, including those related to ELOVL1 and 6, were detected between TN and EP+H-, and it was suggested that ELOVL1 and 6-related fatty acid metabolism pathways may be targets for therapies against TN.
Highlights
Triple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate
The number of targeted metabolites included in the multiple reaction monitoring (MRM) database was 267 of hydrophilic metabolites and 284 of hydrophobic lipid metabolites (Additional file 1: Table S1, Additional file 2: Table S2 and Additional file 3: Table S3), and we identified 142 of hydrophilic metabolites and 278 of hydrophobic lipid metabolites in breast cancer tissue samples and the corresponding normal breast tissue samples
We confirmed the association between the identified metabolites and metabolite pathways by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Database, and evaluations based on the glycolytic pathway, tricarboxylic acid (TCA) cycle, glutamine pathway, choline pathway, urea cycle, tryptophan cycle, glutathione cycle, purine pathway, pyrimidine pathway, and amino acid metabolism were carried out (Table 2A)
Summary
Triple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Most breast cancer subtypes are ER-positive [4], but approximately 15–20% do not express ER, PgR, or HER2. These are known as triple-negative breast cancer (TN). TN is associated with a high recurrence rate, distant metastasis, and a poor survival It is the most aggressive breast cancer [5, 6]. It is necessary to understand the characteristics of TN to aid the development of effective systemic treatments for the disease
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