Fasting hyperglycaemia and fatty liver drive colorectal cancer: a retrospective analysis in 1145 patients

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the hepatic manifestation of increased adiposopathy, whose pathogenetic features have been proposed as tumourigenic triggers for colorectal cancer (CRC). We aim to identify specific metabolic signatures involved in CRC development that may be used as non-invasive biomarkers, paving the way for specific and personalized strategies of CRC prevention and early detection. Methods: We retrospectively assessed CRC onset during a time frame of 8 years in a cohort of 1145 out-patients individuals who had previously been evaluated for Metabolic Syndrome. Results: 28 patients developed CRC. No association between CRC development and visceral and general obesity was detected, while baseline fasting plasma glucose (FPG) and non-invasive liver fibrosis scores were significantly higher in patients with CRC, compared to those who did not develop cancer. Liver steatosis and MASLD were more frequently diagnosed in patients who developed CRC compared to no cancer developers. Canonical correlations among metabolic biomarkers were not present in CRC developers, differently from no cancer group. In ROC analysis, FPG and non-invasive scores also showed good sensitivity and specificity in predicting colon cancer. We then calculated ORs for metabolic biomarkers, finding that higher FPG and non-invasive scores were associated with an increased risk of developing CRC. Conclusion: MASLD and increased FPG may play a role in the clinical background of CRC, bringing to light the fascinating possibility of a reversed gut-liver axis communication in the pathogenesis of CRC. Thus, the use of non-invasive scores of fatty liver may be helpful to predict the risk of CRC and serve as novel prognostic factors for prevention and therapeutic strategies.