vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2023-20-2-112-125vestim-909Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEЗначимость фрагмента цитокератина-19 и рецепторов CXCR1, CXCR2 в крови для прогнозирования безрецидивной выживаемости пациентов с III стадией немелкоклеточного рака легкогоSignificance of the cytokeratin-19 fragment and CXCR1, CXCR2 receptors in the blood for prediction of the relapse-free survival of patients with stage III non-small cell lung cancerТагановичА. Д.TahanovichA. D.

Таганович Анатолий Дмитриевич – д-р мед. наук, профессор, заведующий кафедрой

пр. Дзержинского, 83, 220116, г. Минск

Anatoli D. Tahanovich – D. Sc. (Med.), Professor, Head of the Department

83, Dzerzhinski Ave., 220116, Minsk

ataganovich@gmail.comКовганкоН. Н.KauhankaN. N

Ковганко Николай Николаевич – канд. хим. наук, доцент

пр. Дзержинского, 83, 220116, г. Минск

Nikolai N. Kauhanka – Ph. D. (Chem.), Associate Professor

83, Dzerzhinski Ave., 220116, Minsk

mikalai44@tut.byПрохороваВ. И.ProkhorovaV. I.

Прохорова Виолетта Игоревна – д-р мед. наук, профессор, заведующий лабораторией

223040, а/г Лесной, Минский р-н

Violetta I. Prokhorova – D. Sc. (Med.), Professor, Head of the Laboratory

223040, Lesnoy, Minsk region

vprohorova@mail.ruКолбА. В.KolbA. V.

Колб Александр Владимирович – канд. биол. наук, доцент

пр. Дзержинского, 83, 220116, г. Минск

Alexander V. Kolb – Ph. D. (Biol.), Associate Professor

83, Dzerzhinski Ave., 220116, Minsk

sanya.kolb@yandex.byГотькоО. В.Got’koO. V.

Готько Оксана Владимировна – ст. науч. сотрудник

223040, а/г Лесной, Минский р-н

Oksana V. Got’ko – Senior Researcher

223040, Lesnoy, Minsk region

babuka_05@mail.ruБелорусский государственный медицинский университетBelarusian State Medical UniversityРеспубликанский научно-практический центр онкологии и медицинской радиологии им. Н. Н. АлександроваN. N. Alexandrov National Cancer Centre202305062023202112125Copyright © Таганович А.Д., Ковганко Н.Н., Прохорова В.И., Колб А.В., Готько О.В., 20232023Таганович А.Д., Ковганко Н.Н., Прохорова В.И., Колб А.В., Готько О.В.Tahanovich A.D., Kauhanka N.N., Prokhorova V.I., Kolb A.V., Got’ko O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/909

Немелкоклеточный рак легкого (НМКРЛ) в III стадии представляет собой неоднородную группу опухолей. Прогноз для пациентов с III стадией НМКРЛ остается плохим, а 5-летняя выживаемость составляет не более 20 %. Поэтому актуальной является необходимость разработки прогнозных показателей, которые позволили бы предсказывать прогрессирование опухолевого процесса, чтобы оптимизировать стратегию и тактику лечения пациентов.

Целью исследования являлось выяснение и обоснование возможности использования лабораторных показателей, характеризующих уровень белков крови – участников канцерогенеза, в прогнозе прогрессирования НМКРЛ у пациентов с III стадией этого заболевания.

У 1187 пациентов с впервые диагностированным НМКРЛ III стадии проанализирована длительность безрецидивного периода после проведенного лечения по результатам наблюдения в течение одного года. Средний возраст пациентов составил 63 ± 23 года. У 89 пациентов (возраст 58 ± 23,5 года) измерялись концентрации CYFRA 21-1, SCC, TPA электрохемилюминесцентным методом; M2 пируваткиназы, хемокинов CXCL5, CXCL8 – иммуноферментным методом; рецепторов CXCR1 и CXCR2 – методом проточной цитометрии.

С помощью многофакторной модели пропорциональных рисков Кокса обнаружена тесная связь уровня CYFRA 21-1 и доли лимфоцитов, содержащих CXCR1, с длительностью безрецидивного периода у пациентов с III стадией НМКРЛ после проведенного лечения. По итогам одногодичного наблюдения и графического анализа Каплана– Майера определены группы низкого (T1N2M0, T3N1M0, T2N2M0, T4N0M0, T3N2M0) и высокого (T1N3M0, T2N3M0, T3N3M0, T4N1M0, T4N2M0, T4N3M0) риска прогрессирования опухоли. У пациентов с высоким риском по сравнению с пациентами с низким риском больше был уровень CYFRA 21-1, относительное содержание рецептора CXCR1 в лимфоцитах и рецептора CXCR2 в моноцитах (p p < 0,05). С использованием этих показателей по результатам логистического регрессионного анализа построено уравнение, с помощью которого можно прогнозировать риск рецидива опухоли. Пороговое значение уравнения – 0,519. Чувствительность модели построения прогноза – 80,9 %, специфичность – 83,3 %, прогностическая ценность положительного результата – 84,4 %, отрицательного результата – 79,6 %.

Итоги проведенного исследования дают основание рекомендовать измерение у пациентов с III стадией НМКРЛ комплекса лабораторных показателей крови, включающего уровень CYFRA 21-1 и параметры рецепторов CXCR1 и CXCR2, с целью оценки у них риска прогрессирования опухоли.

Stage III non-small cell lung cancer (NSCLC) is a heterogeneous group of tumors. The prognosis for patients with stage III NSCLC remains poor, and the 5-year survival rate is not more than 20 %. Therefore, an actual problem is to develop prognostic indicators that would allow predicting the progression of the tumor process in patients in order to correctly build strategy and tactics for their treatment.

The objective of the study was to clarify and substantiate the possibility of using laboratory parameters characterizing the level of blood proteins – participants in carcinogenesis in predicting the NSCLC progression in patients with stage III disease.

In 1187 patients who were first diagnosed with stage III NSCLC, the duration of the relapse-free period after treatment was analyzed using the observation results for one year. The mean age of patients was 63 ± 23 years. In 89 patients (58 ± 23.5 years), the concentration of CYFRA 21-1, SCC, TPA were determined by electrochemiluminescent method; pyruvate kinase M2, CXCL5, CXCL8 chemokines – by enzyme immunoassay; CXCR1 and CXCR2 receptors– by flow cytometry.

A proportional hazards model was used to identify potentially informative indicators for predicting the duration of the relapse-free period in patients with stage III NSCLC: the levels of lymphocytes containing CXCR1 and CYFRA 21-1. Based on the one-year observation results and the graphical analysis of Kaplan-Meier, groups of low (T1N2M0, T3N1M0, T2N2M0, T4N0M0, T3N2M0) and high (T1N3M0, T2N3M0, T3N3M0, T4N1M0, T4N2M0, T4N3M0) risk of tumor progression were identified. High-risk patients had a higher level of CYFRA 21-1, a relative content of the receptor CXCR1 in lymphocytes, and a relative content of the receptor CXCR2 in monocytes compared to low-risk patients (p < 0.05). With their participation, based on the results of logistic regression analysis, an equation was constructed, the calculation of which makes it possible to predict the risk of tumor recurrence. The threshold value of the equation is 0.519. The sensitivity of the prediction model was 80.9 %, the specificity was 83.3 %, and the prediction value of a positive result was 84.4 % and that of a negative result – 79.6 %. The study results give grounds to recommend a set of laboratory parameters in the blood of stage III NSCLC patients, including the CYFRA 21-1 level and the receptors CXCR1 and CXCR2, in order to assess their tumor progression risk.>< 0.05). With their participation, based on the results of logistic regression analysis, an equation was constructed, the calculation of which makes it possible to predict the risk of tumor recurrence. The threshold value of the equation is 0.519. The sensitivity of the prediction model was 80.9 %, the specificity was 83.3 %, and the prediction value of a positive result was 84.4 % and that of a negative result – 79.6 %.

The study results give grounds to recommend a set of laboratory parameters in the blood of stage III NSCLC patients, including the CYFRA 21-1 level and the receptors CXCR1 and CXCR2, in order to assess their tumor progression risk.

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The authors declare that there are no conflicts of interest present.