Abstract

BackgroundWe have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples.MethodsPlasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)–electrospray ionization (ESI)–mass spectrometry (MS).ResultsHigh reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers.ConclusionsThese findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer.

Highlights

  • We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a plasma free amino acids (PFAAs)-based, multivariate discrimination index for the early detection of lung cancer

  • Plasma free amino acids (PFAAs), which are abundant in the circulation and link all organ systems, are favorable targets because PFAA profiles are influenced by metabolic variations in specific organ systems induced by specific diseases [13,14,15,16,17,18]

  • We found that changes in PFAA profiles that were common to all types of cancer as well as those specific to individual cancers [34] .These functions are used in the “AminoIndexW Cancer Screening” service in Japan

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Summary

Introduction

We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. We aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples. Computer-aided systems for data mining, (e.g., using multivariate analysis) are readily available and have shown promising results when applied to metabolic profiles for diagnostic and clinical use [4,5,6]. Several investigators have reported changes in PFAA profiles in cancer patients, including lung cancer patients [19,20,21,22,23,24,25,26,27]. Several discrepancies exist between the results of these studies due to the limited size of the data set [22]

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