Tissue amino acid profile could be used to differentiate advanced adenoma from colorectal cancer

Advanced adenomas are of higher risk to progress to colorectal cancer (CRC), the third leading cause of cancerous death worldwide. Endoscopy-based adenoma removal greatly contributes to arresting the progression of adenoma to CRC. Precise diagnosis, post-polypectomy surveillance and the follow-up clinical decisions predominantly depend on histopathologic inspection of the resected tissues. The common artificial histological inspection is not fully reliable and is only compatible with the en bloc removed tissues. An alternative measure ensuring more objective tissue malignance appraisal, which is applicable to various endoscopically acquired sample types are highly appreciated. In this study, we firstly employed capillary electrophoresis-mass spectrometry-based untargeted metabolomic technique to analyze CRC and corresponding paracancerous tissues to narrow the scope of malignancy-related metabolite changes. The primary results implied the most perturbated metabolites by CRC onset were amino acids. Subsequently, a targeted amino acid analysis by ultra-performance liquid chromatography-mass spectrometry indicated 9 amino acids were of different content between advanced adenoma and CRC tissues. Finally, regression analysis of the 9 differential amino acids exhibited that methionine, tyrosine, valine and isoleucine could be used to differentiate CRC from advanced adenomas with good sensitivity and specificity (p<0.001). Area under the receiver operating characteristic curve was 0.991. This study demonstrated the utility of metabolomic analysis in assisting malignance evaluation of colorectal neoplasia and the potential value of amino acids analysis in clinical pathology practice.