Profiling the metabolic disorder and detection of colorectal cancer based on targeted amino acids metabolomics

BackgroundThe morbidity of cancer keeps growing worldwide, and among that, the colorectal cancer (CRC) has jumped to third. Existing early screening tests for CRC are limited. The aim of this study was to develop a diagnostic strategy for CRC by plasma metabolomics.MethodsA targeted amino acids metabolomics method was developed to quantify 32 plasma amino acids in 130 CRC patients and 216 healthy volunteers, to identify potential biomarkers for CRC, and an independent sample cohort comprising 116 CRC subjects, 33 precancerosiss patients and 195 healthy volunteers was further used to validate the diagnostic model. Amino acids-related genes were retrieved from Gene Expression Omnibus and Molecular Signatures Database and analyzed.ResultsThree were chosen out of the 32 plasma amino acids examined. The tryptophan / sarcosine / glutamic acid -based receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of 0.955 (specificity 83.3% and sensitivity 96.8%) for all participants, and the logistic regression model were used to distinguish between early stage (I and II) of CRC and precancerosiss patients, which showed superiority to the commonly used carcinoembryonic antigen. The GO and KEGG enrichment analysis proved many alterations in amino acids metabolic pathways in tumorigenesis.ConclusionThis altered plasma amino acid profile could effectively distinguish CRC patients from precancerosiss patients and healthy volunteers with high accuracy. Prognostic tests based on the tryptophan/sarcosine/glutamic acid biomarkers in the large population could assess the clinical significance of CRC early detection and intervention. The targeted amino acids metabolomics was applied to profile the alterations of amino acids in colorectal cancer.Plasma amino acids profile shows capability of differentiating the colorectal cancer from the precancerosiss patients and healthy volunteersA diagnostic model Y = 0.001xTrp +0.029xSar-0.002xGlu-9.427 (unit: ng/mL) was developed and validated for colorectal cancer diagnosis.Amino acids-related differentially expressed genes analysis supported the alterations of amino acids metabolic profile in tumorigenesis.