Comprehensive Volatilome and Metabolome Signatures of Colorectal Cancer in Urine: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Colorectal cancer is the most frequent neoplasm in Western countries, the second most frequent neoplasm after breast cancer in women and the third most frequent neoplasm after prostate and lung cancer in men. Early diagnosis and disease screening are based on a fecal occult blood test, which, if positive, is complemented by colonoscopy. Currently, efforts are underway to find alternatives to the fecal occult blood test for various reasons. First, there is an ongoing attempt to increase the participation of the population to be screened. Second, there is a need to decrease the number of false positives to reduce the number of unnecessary colonoscopies. A urine test could be more widely accepted than a fecal test, and this is the scenario for which urinary metabolomics and volatilome studies are being developed. Our review provides the first exhaustive evaluation of metabolomics and volatilomics for the determination of colorectal cancer in urine. ABSTRACT: To increase compliance with colorectal cancer screening programs and to reduce the recommended screening age, cheaper and easy non-invasiveness alternatives to the fecal immunochemical test should be provided. Following the PRISMA procedure of studies that evaluated the metabolome and volatilome signatures of colorectal cancer in human urine samples, an exhaustive search in PubMed, Web of Science, and Scopus found 28 studies that met the required criteria. There were no restrictions on the query for the type of study, leading to not only colorectal cancer samples versus control comparison but also polyps versus control and prospective studies of surgical effects, CRC staging and comparisons of CRC with other cancers. With this systematic review, we identified up to 244 compounds in urine samples (3 shared compounds between the volatilome and metabolome), and 10 of them were relevant in more than three articles. In the meta-analysis, nine studies met the criteria for inclusion, and the results combining the case-control and the pre-/post-surgery groups, eleven compounds were found to be relevant. Four upregulated metabolites were identified, 3-hydroxybutyric acid, L-dopa, L-histidinol, and N1, N12-diacetylspermine and seven downregulated compounds were identified, pyruvic acid, hydroquinone, tartaric acid, and hippuric acid as metabolites and butyraldehyde, ether, and 1,1,6-trimethyl-1,2-dihydronaphthalene as volatiles.