[Structural and functional parameters of erythrocytes as predictors of unfavorable outcome in patients with colorectal cancer].

Aim: Identification the characteristics of fatty acids (FAs) in erythrocyte membranes and in blood serum, as well as the electrical and viscoelastic parameters of erythrocytes to assess their ability to be predictors of an unfavorable outcome in patients with colorectal cancer (CRC).

Materials and methods: 112 people with an average age of 63.1 ± 9.5 years (62 men, 50 women) with CRC of stages I-IV were examined. The patients were divided into 2 groups depending on the outcome of the disease after 6 years of follow-up: group 1 - with stabilization of the disease (n = 55), group 2 (n = 57) - with an unfavorable outcome. The FA composition of erythrocyte membranes and blood serum was studied using gas chromatography/mass spectrometry, a system based on three Agilent 7000B quadrupoles (USA). The electrical and viscoelastic parameters of erythrocytes were studied using the method of dielectrophoresis.

Results: An unfavorable outcome in patients with CRC is associated with elevated levels of docosapentaenoic acid (C22:5n-3) (p = 0.0003), docosahexaenoic acid (C22:6n-3) (p = 0.001), docosathetraenoic acid (C22:4n-6) (p = 0.004), and total omega-3 polyunsaturated fatty acids (PUFA) (p = 0.0004) in erythrocyte membranes, eicosadienoic acid (C20:2 n-6) in erythrocyte membranes (p = 0.03) and blood serum (p = 0.01), and, conversely, reduced levels of ratios saturated fatty acids (SFA)/PUFA (p = 0.004), SFA / unsaturated fatty acids (USFA) (p = 0.01) and concentrations of myristic FA (C14:0) (p = 0.03) in erythrocyte membranes, as well as with a number of changes in electrical, viscoelastic parameters of red blood cells: with increased hemolysis of red blood cells at high frequencies (10⁶ Hz - p = 0.0006 and 5 × 10⁵ Hz - p = 0.046), increased aggregation indices at low frequencies (10⁵ Hz - p = 0.04 and 5 × 10⁴ Hz - p = 0.047), as well as a shift in the crossover frequency to the high frequency range (p = 0.036). In patients with stages 1-2 of CRC, omega-6 PUFAs, eicosadienoic acid C20:2n-6 (p = 0.006), docosatetraenoic acid C22:4n-6 (p = 0.012), were of the greatest importance for differentiating disease outcomes, while total content omega-3 PUFAs in erythrocyte membranes (p = 0.0129), docosahexaenoic acid C22:6 n-3 (p = 0.0169), total content (C20:5n-3+C22:6n-3) in erythrocyte membranes (p = 0.0198), docosapentaenoic acid C22:5 n-3 (p = 0.022) were slightly less important. As in the general group of patients with CRC, the degree of hemolysis at a frequency of 10⁶ Hz was a predictor of an unfavorable outcome in people with early stages of the oncological process. ROC analysis revealed a high potential of palmitic acid in erythrocyte membranes to predict an unfavorable CRC outcome (AUC 0.786, 95% confidence interval 0.638-0.901, sensitivity 84.4%, specificity 68.2%). The diagnostic model, which included five parameters - erythrocyte levels C16:0, ratio SFA/PUFA, total USFA, total PUFA, and serum levels C20:2n-6, had an AUC of 0.663 (95% confidence interval 0.483-0.801) with the highest sensitivity of 85.2%, but not high specificity of 60.1% for predicting an unfavorable outcome in CRC.

Conclusion: Fatty acids of erythrocyte membranes, blood serum, electrical, and viscoelastic parameters of erythrocytes should be considered as promising biomarker predictors in patients with CRC that require further study.