Kruchinina M V, Osipenko M F, Gromov A A, Starikov A V
Research Institute of Internal and Preventive Medicine.
Novosibirsk State Medical University.
Ter Arkh. 2025 Aug 28;97(8):668-679. doi: 10.26442/00403660.2025.08.203336.
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).
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 ( = 55), group 2 ( = 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.
An unfavorable outcome in patients with CRC is associated with elevated levels of docosapentaenoic acid (C22:5n-3) ( = 0.0003), docosahexaenoic acid (C22:6n-3) ( = 0.001), docosathetraenoic acid (C22:4n-6) ( = 0.004), and total omega-3 polyunsaturated fatty acids (PUFA) ( = 0.0004) in erythrocyte membranes, eicosadienoic acid (C20:2 n-6) in erythrocyte membranes ( = 0.03) and blood serum ( = 0.01), and, conversely, reduced levels of ratios saturated fatty acids (SFA)/PUFA ( = 0.004), SFA / unsaturated fatty acids (USFA) ( = 0.01) and concentrations of myristic FA (C14:0) ( = 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 (10Hz - = 0.0006 and 5 × 10Hz - = 0.046), increased aggregation indices at low frequencies (10Hz - = 0.04 and 5 × 10Hz - = 0.047), as well as a shift in the crossover frequency to the high frequency range ( = 0.036). In patients with stages 1-2 of CRC, omega-6 PUFAs, eicosadienoic acid C20:2n-6 ( = 0.006), docosatetraenoic acid C22:4n-6 ( = 0.012), were of the greatest importance for differentiating disease outcomes, while total content omega-3 PUFAs in erythrocyte membranes ( = 0.0129), docosahexaenoic acid C22:6 n-3 ( = 0.0169), total content (C20:5n-3+C22:6n-3) in erythrocyte membranes ( = 0.0198), docosapentaenoic acid C22:5 n-3 ( = 0.022) were slightly less important. As in the general group of patients with CRC, the degree of hemolysis at a frequency of 10Hz 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.
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.
确定红细胞膜和血清中脂肪酸（FAs）的特征，以及红细胞的电学和粘弹性参数，以评估它们作为结直肠癌（CRC）患者不良预后预测指标的能力。
对112例年龄平均为63.1±9.5岁（62名男性，50名女性）的I-IV期CRC患者进行了检查。根据6年随访后的疾病结局，将患者分为2组：第1组 - 疾病稳定（n = 55），第2组（n = 57） - 预后不良。使用气相色谱/质谱法研究红细胞膜和血清中的FA组成，该系统基于三个安捷伦7000B四极杆（美国）。使用介电泳方法研究红细胞的电学和粘弹性参数。
CRC患者的不良预后与红细胞膜中二十二碳五烯酸（C22:5n-3）（p = 0.0003）、二十二碳六烯酸（C22:6n-3）（p = 0.001）、二十二碳四烯酸（C22:4n-6）（p = 0.004）和总ω-3多不饱和脂肪酸（PUFA）（p = 0.0004）水平升高有关，与红细胞膜中二十碳二烯酸（C20:2 n-6）（p = 0.03）以及血清中二十碳二烯酸（C20:2 n-6）（p = 0.01）水平升高有关，相反，与红细胞膜中饱和脂肪酸（SFA）/PUFA比值（p = 0.004）、SFA / 不饱和脂肪酸（USFA）比值（p = 0.01）以及肉豆蔻酸（C14:0）浓度（p = 0.03）降低有关，还与红细胞的一些电学、粘弹性参数变化有关：高频（10Hz - p = 0.0006和5×10Hz - p = 0.046）下红细胞溶血增加、低频（10Hz - p = 0.04和5×10Hz - p = 0.047）下聚集指数增加，以及交叉频率向高频范围偏移（p = 0.036）。在I-2期CRC患者中，ω-6多不饱和脂肪酸、二十碳二烯酸C20:2n-6（p = 0.006）、二十二碳四烯酸C22:4n-6（p = 0.012）对于区分疾病结局最为重要，而红细胞膜中总ω-3多不饱和脂肪酸含量（p = 0.0129）、二十二碳六烯酸C22:6 n-3（p = 0.0169）、红细胞膜中总含量（C20:5n-3 + C22:6n-3）（p = 0.0198）、二十二碳五烯酸C22:5 n-3（p = 0.022）的重要性稍低。与CRC患者总体情况一样，10Hz频率下的溶血程度是肿瘤进程早期患者不良预后的预测指标。ROC分析显示红细胞膜中棕榈酸预测CRC不良预后具有较高潜力（AUC 0.786，95%置信区间0.638 - 0.901，敏感性84.4%，特异性68.2%）。包含五个参数 - 红细胞水平C16:0、SFA/PUFA比值、总USFA、总PUFA以及血清水平C20:2n-6的诊断模型，预测CRC不良预后的AUC为0.663（95%置信区间0.483 - 0.801），敏感性最高为85.2%，但特异性不高，为60.1%。
红细胞膜脂肪酸、血清、红细胞的电学和粘弹性参数应被视为CRC患者中有前景的生物标志物预测指标，需要进一步研究。
