5774 - A joint metabolic profile of plasma and tissue samples for discovering novel biomarkers in breast cancer

Background

The dysregulated tumour metabolism is one of the hallmarks of cancer. Metabolome analysis has thus been proposed as a broadly applicable tool for diagnosis and anti-cancer treatment in various cancers, such as lung, colorectal and breast cancers. Up until now, a number of metabolic biomarkers have been reported; however, there is still little application in a clinical setting due to the fact that the metabolic approach with the clinical samples has not been generally authorized. In this study, using metabolome analysis, we determined the cancer-specific metabolites and explored the applicability of the liquid biopsy for discovering the potential biomarkers of breast cancer.

Methods

A total of 22 patients with breast cancer were enrolled and their metabolite levels were analyzed with CE-MS, quantitating 511 identifiable metabolites in plasma and non-cancer/cancer tissues. Samples were immediately kept in liquid nitrogen and stored at -80˚C until further tissue processing, including removal of proteins prior to CE-MS analysis. All the available metabolite data with absolute concentration were analyzed using a web-based platform, MetaboAnalyst 4.0.

Results

A total of 511 known metabolites were measured; of these, 159 metabolite changes in concentration were observed in cancer tissues compared with in non-cancer tissues. In plasma samples, 67/159 metabolites significantly increased in cancer tissues. The affected metabolites were 2-hydroxyglutarate, succinate and fumarate, all of which are known as representative "oncometabolites" involved in tumorigenesis. Moreover, metabolites associated with purine synthesis and pyrimidine synthesis were also markedly upregulated. These cancer-related metabolic changes had correlation with the proliferation markers of cancer tissues.

Conclusions

We identified for the first time the signature of metabolic reprograming between non-cancer and cancer tissues in breast cancer, and this metabolic shift was observed in plasma. The plasma levels of biomarkers relating to nucleic acid synthesis (purine and pyrimidine synthesis) was associated with the high proliferation status of breast cancer.

Clinical trial identification

Legal entity responsible for the study

Narumi Harada.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.