This study aimed to characterize the
ATP-synthesis by oxidative phosphorylation in
colorectal cancer (CRC) and premalignant colon
polyps in relation to molecular
biomarkers KRAS and BRAF. This prospective study included 48 patients. Resected colorectal
polyps and postoperative CRC tissue with adjacent normal tissue (control) were collected. Patients with
polyps and CRC were divided into three molecular groups: KRAS mutated, BRAF mutated and KRAS/BRAF wild-type. Mitochondrial respiration in permeabilized tissue samples was observed using high resolution respirometry.
ADP-activated respiration rate (Vmax) and an apparent affinity of mitochondria to
ADP, which is related to mitochondrial outer membrane (MOM) permeability, were determined. Clear differences were present between molecular groups. KRAS mutated CRC group had lower Vmax values compared to wild-type; however, the Vmax value was higher than in the control group, while MOM permeability did not change. This suggests that KRAS mutation status might be involved in acquiring oxidative phenotype. KRAS mutated
polyps had higher Vmax values and elevated MOM permeability as compared to the control. BRAF mutated CRC and
polyps had reduced respiration and altered MOM permeability, indicating a glycolytic phenotype. To conclude, prognostic
biomarkers KRAS and BRAF are likely related to the metabolic phenotype in CRC and
polyps. Assessment of the
tumor mitochondrial
ATP synthesis could be a potential component of patient risk stratification.