Plasma Fatty Acids Depletion in Colon Cancer: A Metabolic Signature Unrelated to Tumour Progression (Preprint)

Abstract

[eng] Background: Patients with colon cancer have decreased plasma fatty acids, yet few studies have undertaken a systemic approach to understand this phenomenon, which could contribute to the design of nutritional interventions. Methods: Patients with colon cancer (stages pT2, pT3 and pT4) (n=172) and healthy controls with confirmed absence of colon cancer or inflammatory bowel disease (n=17) were recruited for this case-control study at the University Hospital Son Espases (Palma, Spain). Plasma fatty acid profile was analysed by gas chromatography-mass spectrometry and body composition was analysed using computerized tomography scans. Tumour tissue underwent transcriptomic analysis for stratification into a consensus molecular subtype (CMS). Findings: A total of 172 patients with colon cancer (median age (IQR), 73 (67-81) years, 53.5% men) and 17 healthy volunteers (median age (IQR), 58 (47-62) years, 58.8% men) were included. Patients with colon cancer had significantly decreased total plasma fatty acids (1583.8 nmol/ml vs. 3867.7 nmol/ml in controls, p<.001). This reduction was consistent across all species, with a ≥50% decrease compared to controls (independent of sex, age, and body mass index). CMS classification revealed significant differences in fatty acid levels, resulting in an elevated ratio of unsaturated to saturated fatty acids in CMS2 (1.67, p=.01). Interpretation: This case-control study confirms that patients with colon cancer have reduced plasma fatty acids and suggests it is an intrinsic metabolic alteration of cancer pathology. Further research will aid clinical significance and guide potential intervention strategies.