Plasma Free Amino Acid Profiling of Five Types of Cancer Patients and Its Application for Early Detection

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.

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

“…The water‐soluble fractions were concentrated 10‐fold using a centrifugal evaporator and applied to the amino acid analysis. Amino acid concentrations in kidney homogenates were measured using high performance liquid chromatography‐electron spray ionization‐mass spectrometry (MS)‐MS (HPLC‐ESI‐MS/MS), followed by precolumn derivatization (Kume et al., 2014; Miyagi et al., 2011; Shimbo, Yahashi, Hirayama, Nakazawa, & Miyano, 2009). …”

Real-Time Quantification of Amino Acids in the Exhalome by Secondary Electrospray Ionization–Mass Spectrometry: A Proof-of-Principle Study

“…Accordingly, plasma free amino acid (PFAA) 6 profiles have become a powerful tool for diagnosis over the past few years. The predictive value of amino acid profiles have been demonstrated for diseases such as cancer (1,2 ), type-2 diabetes (3)(4)(5), and Alzheimer disease (6 ). Among PFAAs, branched-chain amino acids (BCAA), i.e., L, I, and V, have been studied more extensively because of their unique skeletal muscle metabolism.…”

Plasma amino acid profiles in healthy East Asian subpopulations living in Japan

“…Although AA metabolism is strictly regulated in healthy individuals, reports have indicated that certain diseases influence plasma free amino acid (PFAA) profiles (Holm et al, 1999; Hong et al, 1998; Miyagi et al, 2011; Felig et al, 1970). Based on these PFAA characteristics, “AminoIndex Technology,” which can evaluate specific health conditions and disease possibilities by analyzing PFAA status, has recently been described (Miyagi et al, 2011; Okamoto 2011). …”