Stratification of cancer and diabetes based on circulating levels of formate and glucose

Matthias Pietzke†,
Salvador Fernandez Arroyo†,
David Sumpton,
Gillian M. Mackay,
Begoña Martin-Castillo,
Jordi Camps,
Jorge Joven,
Javier A. Menendez,
Alexei VazquezEmail author View ORCID ID profile and
On behalf of the METTEN study group

†Contributed equally

Cancer & Metabolism20197:3

https://doi.org/10.1186/s40170-019-0195-x

Received: 21 December 2018
Accepted: 20 March 2019
Published: 24 April 2019

Abstract

Background

Serum and urine metabolites have been investigated for their use as cancer biomarkers. The specificity of candidate metabolites can be limited by the impact of other disorders on metabolite levels. In particular, the increasing incidence of obesity could become a significant confounding factor.

Methods

Here we developed a multinomial classifier for the stratification of cancer, obesity and healthy phenotypes based on circulating glucose and formate levels. We quantified the classifier performance from the retrospective analysis of samples from breast cancer, lung cancer, obese individuals and healthy controls.

Results

We discovered that circulating formate levels are significantly lower in breast and lung cancer patients than in healthy controls. However, the performance of a cancer classifier based on formate levels alone is limited because obese patients also have low serum formate levels. By introducing a multinomial classifier based on circulating glucose and formate levels, we were able to improve the classifier performance, reaching a true positive rate of 79% with a false positive rate of 8%.

Conclusions

Circulating formate is reduced in HER2+ breast cancer, non-small cell lung cancer and highly obese patients relative to healthy controls. Further studies are required to determine the relevance of these observations in other cancer types and diseases.