New Metabolic Biomarkers May Improve the Ability to Predict Breast Cancer Recurrence

By: Gavin Calabretta, BS
Posted: Thursday, February 9, 2023

A team of researchers, including Susan E. Waltz, PhD, of the University of Cincinnati College of Medicine, found that the RON and DEK proteins may regulate certain metabolic pathways that have previously been linked to cancer progression. Published in PLOS One, the investigators’ findings also identified a signature based on these pathways that may aid in the ability to predict recurrence of breast cancer.

“We showed that both RON and DEK are very important in breast cancer and that both...are independently associated with poor overall survival in breast cancer patients,” commented Dr. Waltz in an institutional press release. The team believes the metabolic pathways regulated by these proteins may provide new therapeutic targets.

The researchers used a nuclear magnetic resonance–based metabolomics approach to study different metabolic pathways and attempted to stratify patient outcomes using genes from those modulated by RON/DEK/b-catenin. Genes that significantly stratified relapse-free survival and distant metastasis–free survival were used to create a signature, which the researchers validated using data sets from The Cancer Genome Atlas and the Gene Expression Omnibus. A separate, combined signature was also created, which incorporated RON/DEK/b-catenin expression along with the metabolic genes. Both were tested in their capacity to predict chemotherapy response in patients with node-positive breast cancer.

The study implicated b-catenin in the regulation of glycolysis, glycosylation, the TCA cycle, NAD-positive production, and creatine dynamics. Genes in these pathways that were epistatic to RON-DEK-b-catenin primarily defined the metabolism signature. When the investigators classified recurrence-free survival, the metabolism signature achieved a larger hazard ratio (HR) (HR = 1.77) than the RON/DEK/b-catenin signature (HR = 1.48), suggesting a greater extent of stratification. However, the combined signature scored highest (HR = 1.81). This was also true regarding distant metastasis–free survival, with the combined signature (HR = 2.07) followed by the RON/DEK/b-catenin signature (HR = 1.82) and the metabolism signature (HR = 1.77). The combined signature, similarly, showed the best predictive ability for treatment response.

Disclosure: No disclosure information was provided.

PLOS One

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