Terapevticheskii arkhivTerapevticheskii arkhivТерапевтический архив0040-36602309-5342LLC Obyedinennaya Redaktsiya68009110.26442/00403660.2025.08.203336Original articlesОригинальные статьиResearch ArticleStructural and functional parameters of erythrocytes as predictors of unfavorable outcome in patients with colorectal cancerСтруктурно-функциональные параметры эритроцитов как предикторы неблагоприятного исхода у пациентов с колоректальным ракомhttps://orcid.org/0000-0003-0077-3823KruchininaMargarita V.КручининаМаргарита Витальевна
Russian Federation

д-р мед. наук, проф., зав. лаб. гастроэнтерологии, вед. науч. сот. лаб. гастроэнтерологии; проф. каф. пропедевтики внутренних болезней

kruchmargo@yandex.ruhttps://orcid.org/0000-0002-5156-2842OsipenkoMarina F.ОсипенкоМарина Федоровна
Russian Federation

д-р мед. наук, проф., зав. каф. пропедевтики внутренних болезней

kruchmargo@yandex.ruhttps://orcid.org/0000-0001-9254-4192GromovAndrey A.ГромовАндрей Александрович
Russian Federation

канд. мед. наук, ст. науч. сотр. лаб. клинических биохимических и гормональных исследований терапевтических заболеваний, руководитель Центра профилактики тромбозов

kruchmargo@yandex.ruhttps://orcid.org/0009-0009-6776-3401StarikovAndrey V.СтариковАндрей Владимирович
Russian Federation

врач-онколог

kruchmargo@yandex.ruResearch Institute of Internal and Preventive MedicineНаучно-исследовательский институт терапии и профилактической медициныNovosibirsk State Medical UniversityНовосибирский государственный медицинский университетNovosibirsk Regional Oncology DispensaryНовосибирский областной онкологический диспансер28082025978Treatment issuesВопросы лечения6686792105202502062025Copyright ©; 2025, Consilium MedicumCopyright ©; 2025, ООО "Консилиум Медикум"2025Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://ter-arkhiv.ru/0040-3660/article/view/680091

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.

Цель. Выявить особенности жирных кислот в мембранах эритроцитов и сыворотке крови, электрические и вязкоупругие параметры эритроцитов для оценки их способности быть предикторами неблагоприятного исхода у пациентов с колоректальным раком (КРР).

Материалы и методы. Обследованы 112 человек – средний возраст 63,1 ± 9,5 года (62 мужчины, 50 женщин) с КРР I–IV стадий. Пациенты разделены на 2 группы в зависимости от исхода заболевания через 6 лет наблюдения: 1-я группа – со стабилизацией заболевания (n = 55), 2-я группа (n = 57) – с неблагоприятным исходом. Исследование жирных кислот (ЖК) состава мембран эритроцитов, сыворотки крови проведено с помощью газовой хроматографии/масс-спектрометрии – системы на основе трех квадруполей Agilent 7000B (США). Электрические, вязкоупругие параметры эритроцитов изучены с использованием метода диэлектрофореза.

Результаты. Неблагоприятный исход у пациентов с КРР ассоциирован с повышенными уровнями докозапентаеновой С22:5n-3 (p = 0,0003), докозагексаеновой С22:6n-3 (p = 0,001), докозатетраеновой С22:4n-6 (p = 0,004), суммарного содержания омега-3 полиненасыщенных жирных кислот (ПНЖК) (p = 0,0004) в мембранах эритроцитов, эйкозадиеновой кислоты (C20:2n-6) в мембранах эритроцитов (p = 0,03) и сыворотке крови (p = 0,01) и, напротив, сниженными уровнями соотношений насыщенные жирные кислоты (НЖК) / ПНЖК (p = 0,004), НЖК / ненасыщенные жирные кислоты (ННЖК) (p = 0,01) и концентрации миристиновой ЖК С14:0 (p = 0,03) в мембранах эритроцитов, а также рядом изменений электрических, вязкоупругих параметров эритроцитов: с повышенным гемолизом эритроцитов на высоких частотах (106 Гц – p = 0,0006 и 5 × 105 Гц – p = 0,046), повышенными индексами агрегации на низких частотах (105 Гц – p = 0,04 и 5 × 104 Гц – p = 0,047), а также смещением равновесной частоты в высокочастотный диапазон (p = 0,036). У пациентов с I–II стадиями КРР наибольшую значимость для дифференцирования исходов заболевания имели омега-6 ПНЖК – эйкозадиеновая кислота C20:2n-6 (p = 0,006), докозатетраеновая кислота С22:4n-6 (p = 0,012), несколько меньшую – омега-3 ПНЖК – суммарное содержание их в мембранах эритроцитов (p = 0,0129), докозагексаеновая кислота С22:6 n-3 (p = 0,0169), суммарное содержание (С20:5n-3 + С22:6n-3) в мембранах эритроцитов (p = 0,0198), докозапентаеновая кислота С22:5n-3 (p = 0,022). Как и в общей группе пациентов с КРР, степень гемолиза на частоте 106 Гц была предиктором неблагоприятного исхода у лиц с ранними стадиями онкологического процесса. При проведении ROC-анализа выявлен высокий потенциал пальмитиновой кислоты в мембранах эритроцитов для предикции неблагоприятного исхода КРР (AUC 0,786, 95% доверительный интервал 0,638–0,901, чувствительность 84,4%, специфичность 68,2%). Диагностическая модель, включающая 5 параметров – эритроцитарные уровни С16:0, НЖК/ПНЖК, ННЖК, ПНЖК и сывороточный уровень С20:2n-6, – имела AUC 0,663 (95% доверительный интервал 0,483–0,801) с наиболее высокой чувствительностью (85,2%), но невысокой специфичностью (60,1%) для прогноза неблагоприятного исхода при КРР.

Заключение. ЖК мембран эритроцитов, сыворотки крови, электрические, вязкоупругие параметры эритроцитов следует рассматривать как перспективные биомаркеры-предикторы у пациентов с КРР, требующие дальнейшего изучения.

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