The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

SIMPLE SUMMARY: Colorectal Cancer (CRC) is one of the leading causes of cancer-related death in the United States. Current diagnosis techniques are either highly invasive or lack sensitivity, suggesting the need for alternative techniques for biomarker detection. Metabolomics represents one such technique with great promise in identifying CRC biomarkers with high sensitivity and specificity, but thus far is rarely employed in a clinical setting. In order to provide a framework for future clinical usage, we characterized dysregulated metabolites across recent literature, identifying metabolites dysregulated across a variety of biospecimens. We additionally put special focus on the interplay of the gut microbiome and perturbed metabolites in CRC. We were able to identify many metabolites showing consistent dysregulation in CRC, demonstrating the value of metabolomics as a promising diagnostic technique. ABSTRACT: Colorectal cancer (CRC) is a highly prevalent disease with poor prognostic outcomes if not diagnosed in early stages. Current diagnosis techniques are either highly invasive or lack sufficient sensitivity. Thus, identifying diagnostic biomarkers of CRC with high sensitivity and specificity is desirable. Metabolomics represents an analytical profiling technique with great promise in identifying such biomarkers and typically represents a close tie with the phenotype of a specific disease. We thus conducted a systematic review of studies reported from January 2012 to July 2021 relating to the detection of CRC biomarkers through metabolomics to provide a collection of knowledge for future diagnostic development. We identified thirty-seven metabolomics studies characterizing CRC, many of which provided metabolites/metabolic profile-based diagnostic models with high sensitivity and specificity. These studies demonstrated that a great number of metabolites can be differentially regulated in CRC patients compared to healthy controls, adenomatous polyps, or across stages of CRC. Among these metabolite biomarkers, especially dysregulated were certain amino acids, fatty acids, and lysophosphatidylcholines. Additionally, we discussed the contribution of the gut bacterial population to pathogenesis of CRC through their modulation to fecal metabolite pools and summarized the established links in the literature between certain microbial genera and altered metabolite levels in CRC patients. Taken together, we conclude that metabolomics presents itself as a promising and effective method of CRC biomarker detection.