Gene Expression-Based Inference of Metabolic Signatures Reveals Distinct Molecular Profiles in Right- and Left-Sided Colon Cancer

Background/Objective: Colon cancer, the third most diagnosed cancer worldwide, is anatomically classified into right- and left-sided colon cancers based on embryonic origin and vascular supply. The aim of this study was to investigate molecular differences between patients with right- and left-sided colon cancer. Methods: In this pilot study, Blood samples from right-sided (n = 6) and left-sided (n = 6) colon cancer patients, as well as healthy controls (n = 6), were analyzed for 92 cancer-related genes via RT-qPCR. KEGG pathway analysis was performed with ShinyGO 0.82, and gene–metabolite interactions were assessed using EnrichR and MetaboAnalyst 6.0. Additionally, patients’ sociodemographic and clinical data were analyzed. Results: KEGG analysis revealed that p53, HIF-1, TNF, PI3K/Akt, MAPK, and Rap1 signaling pathways were enriched in right-sided colon cancer, whereas VEGF, HIF-1, MAPK, PI3K/Akt, Rap1, and Ras signaling pathways were implicated in left-sided colon cancer. In the gene–metabolite analysis, key metabolites identified in right-sided colon cancer included palmitic acid, adenosine triphosphate (ATP), glycerol, and adenosine diphosphate (ADP), associated with genes such as ACSL4, TP53, MAPK14, FLT1, AURKA, KDR, ERCC3, and PFKL. For left-sided colon cancer, glucose-6-phosphate (G6P), ATP, ADP, glycerol, and palmitoyl-CoA were key metabolites forming the basis of the gene–metabolite network, along with genes including G6PD, PFKL, MAPK14, FLT1, CDK4, AURKA, MAP2K1, ERCC3, TP53, WEE1, and GPD2. Conclusions: These findings highlight distinct molecular profiles between right- and left-sided colon cancers, particularly in pathways related to angiogenesis, apoptosis, ferroptosis, and fatty acid metabolism, which may inform therapeutic strategies.