Metabolomic analysis of gut metabolites in patients with colorectal cancer: Association with disease development and outcome

Abstract

Colorectal cancer (CRC) is one of the leading global malignancies with low 5-year survival and high mortality rates. Despite extensive research, the precise role of gut metabolites in CRC development and clinical outcomes remains unclear, while its elucidation may aid the development of improved clinical diagnosis and treatment options. In the present study, targeted metabolomic analysis was conducted on fecal samples from 35 patients with CRC, 37 patients with colorectal adenoma and 30 healthy controls (HC) to identify metabolite biomarkers. Using orthogonal partial least squares discriminant analysis, metabolomic features distinguishing the three groups were identified. Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic utility for distinguishing CRC from HC. The association of gut metabolites with survival in patients with CRC was also analyzed by comparing short-term survivors (STS) and long-term survivors (LTS), and the prognostic ability of metabolites was predicted using Cox regression and Kaplan-Meier analysis. The results of the current study showed that the enriched pathways in CRC included ‘caffeine metabolism’, ‘thiamine metabolism’, ‘phenylalanine, tyrosine and tryptophan biosynthesis’ and ‘phenylalanine metabolism’. ROC analysis found that 9,10-dihydroxy-12-octadecenoic acid, cholesterol ester (18:2) and lipoxinA4 distinguished CRC from HC. Joint quantification of these three metabolites resulted in an area under the ROC curve of 0.969 in the diagnosis of CRC. The analysis of the current study also showed that the expression of metabolites involved in ‘sphingolipid metabolism’ was mainly dysregulated in LTS and STS, while N-acetylmannosamine and 2,5-dihydroxybenzaldehyde were associated with better overall survival. In conclusion, the present study provided preliminary insight into the metabolic changes associated with CRC and may have important implications for the development of future diagnostic and treatment strategies.