RAS mutations and colorectal cancer metabolism: a metabolomic analysis of tissue samples

Colorectal cancer (CRC) is the third most common cancer globally, with incidence and mortality rates projected to rise significantly by 2040. RAS mutations are prevalent in CRC and associated with poor prognosis, yet their role in early-stage CRC remains debated. Metabolomics has revealed metabolic profile differences between CRC patients and healthy individuals, as well as between RAS-mutant and wild-type CRC patients, but the specific roles and mechanisms of metabolites in these groups require further investigation. This study collected 49 CRC tissue samples, including 28 RAS-mutant and 21 wild-type samples. Liquid chromatography - mass spectrometry (LC-MS) was used for metabolite analysis, and multivariate statistical analysis, differential metabolite analysis, and pathway enrichment analysis were employed to compare the metabolic characteristics of the two groups. Multivariate statistical analysis showed relatively large within-group variation but marked differences between the RAS-mutant (M1) and wild-type (W1) groups. Differential metabolite analysis identified 70 upregulated and 134 downregulated metabolites in the M1 group. For example, omega-hydroxy myristic acid and 4 S-hydroxylauric acid were upregulated, while SCHEMBL1056153 and Immepip were downregulated. Correlation analysis revealed relationships between certain metabolites. Pathway enrichment analysis indicated that differentially expressed metabolites were mainly enriched in pathways such as Choline metabolism in cancer, Drug metabolism - cytochrome P450, and beta-Alanine metabolism at KEGG Level 3. Reactome enrichment analysis also revealed associations with specific pathways. This study reveals significant metabolic differences between RAS-mutant and wild-type CRC, identifying key differential metabolites and enriched pathways. These findings enhance the understanding of RAS-mutant CRC metabolism and provide candidate metabolites and pathways that warrant further validation as diagnostic or therapeutic targets. However, the study’s limitations, such as the relatively small sample size, should be considered, and further research is needed to explore the clinical applications and significance of these findings.