Abstract
BackgroundRecently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection.Methods and FindingsPlasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)–electrospray ionization (ESI)–mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling.ConclusionsThese findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods.
Highlights
Several minimally-invasive, easy-to-use cancer diagnostic methods using peripheral blood or urine samples have recently been developed to ease the physical burden on patients and to reduce the costs and time involved [1,2,3,4,5,6,7,8]
These findings suggest that plasma free amino acids (PFAAs) profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis
PFAA profiles can be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods
Summary
Several minimally-invasive, easy-to-use cancer diagnostic methods using peripheral blood or urine samples have recently been developed to ease the physical burden on patients and to reduce the costs and time involved [1,2,3,4,5,6,7,8]. Metabolome analysis is a promising approach in screening for diseases such as cancer, some practical limitations remain. These include the necessity to measure a huge number of metabolites [15,16,17], data-redundancy problems, including the false-discovery rate (FDR) and overfitting, and cost constraints. Rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. The purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection
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