Abstract
Background: Although many studies have demonstrated that plasma metabolic phenotyping allows discriminating between cancer patients and controls, it remains unclear whether different cancer types elicit distinguishable metabolic signatures. Therefore, the present study was designed to examine whether metabolic phenotyping of blood plasma by proton nuclear magnetic resonance spectroscopy allows discriminating between 37 colorectal cancer, 37 breast cancer and 37 lung cancer patients. Material and methods: Plasma proton nuclear magnetic resonance spectra were rationally divided into 110 integration regions defined on the basis of spiking experiments with known metabolites. The normalized integration values of these 110 regions, which represent the metabolic phenotype, were used as statistical variables to construct a classification model which enables to discriminate between the three aforementioned cancer types. Results: The resulting model allows classifying 78% of the colorectal cancer patients, 95% of the breast cancer patients and 84% of the lung cancer patients correctly. Conclusion: This preliminary feasibility study provides strong indications that the plasma metabolic phenotype has potential to become a complementary diagnostic tool to differentiate between cancer types in addition to known general cancer biomarkers.
Highlights
It is widely accepted that cancer cells exhibit a major reprogramming of their energy metabolism in order to fulfill the high metabolic demands that are associated with increased cell proliferation and survival [1]
In order to further explore the ability of the plasma metabolic phenotype to differentiate between cancer types, the present study aims to investigate whether 1H-NMR-based metabolomics of plasma allows to discriminate between colorectal cancer, breast cancer and lung cancer
There were no clusters observed when PCA score plots of the entire patient cohort were stained according to age, Body Mass Index (BMI) or tumor stage, thereby confirming that none of these factors have a confounding effect on the discrimination between colorectal cancer, breast cancer and lung cancer patients (Figures 1B-1D)
Summary
It is widely accepted that cancer cells exhibit a major reprogramming of their energy metabolism in order to fulfill the high metabolic demands that are associated with increased cell proliferation and survival [1]. Because the metabolic alterations in cancer cells provoke changes in the metabolic phenotype of the patient, metabolites might serve as attractive biomarkers for facilitating the diagnosis of cancer. Complex mixtures of metabolites in biofluids, such as plasma, serum or urine, can be mined for diagnostic biomarkers by means of the metabolomics approach. This discipline represents a relatively new ‘omics’ science downstream of genomics, transcriptomics and proteomics that uses an analytical platform in conjunction with multivariate pattern recognition approaches in order to discover and monitor metabolic changes in patient biospecimens related to disease status or in response to a medical or external intervention [2]. The present study was designed to examine whether metabolic phenotyping of blood plasma by proton nuclear magnetic resonance spectroscopy allows to discriminate between 37 colorectal cancer, 37 breast cancer and 37 lung cancer patients
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