medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2023.11.13-19medgen-2369Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHЭкспрессия генов иммунных контрольных точек при прогрессии рака почкиExpression of immune checkpoint genes during kidney cancer progressionАпановичН. В.ApanovichN. V.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechye st., Moscow, 115522

АпановичП. В.ApanovichP. V.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechye st., Moscow, 115522

ХалмурзаевО. А.KhalmurzaevO. A.

115478, г. Москва, Каширское шоссе, д. 23

23, Kashirskoe shosse, Moscow, 115478

МатвеевВ. Б.MatveevV. B.

115478, г. Москва, Каширское шоссе, д. 23

23, Kashirskoe shosse, Moscow, 115478

АлимовА. А.AlimovA. A.

115522, г. Москва, ул. Москворечье, д. 1

1, Moskvorechye st., Moscow, 115522

ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical Genetics n.a. N.P. BochkovRussian FederationФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииРоссияN.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian FederationRussian Federation20230812202322111319Copyright © Апанович Н.В., Апанович П.В., Халмурзаев О.А., Матвеев В.Б., Алимов А.А., 20232023Апанович Н.В., Апанович П.В., Халмурзаев О.А., Матвеев В.Б., Алимов А.А.Apanovich N.V., Apanovich P.V., Khalmurzaev O.A., Matveev V.B., Alimov A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2369

Светлоклеточный почечно-клеточный рак (скПКР) является наиболее распространенным и агрессивным гистологическим подтипом почечно-клеточного рака. На момент постановки диагноза у трети больных имеют место отдаленные метастазы. Значительный прогресс в лечении метастатического рака почки достигнут с началом применения таргетной терапии и терапии ингибиторами иммунных контрольных точек. Тем не менее такая терапия не всегда эффективна. В этой связи актуально изучение молекулярных механизмов, лежащих в основе резистентности и прогрессирования рака почки. В данном исследовании изучены образцы опухоли от пациентов с метастатическим и неметастатическим скПКР. В опухолевой ткани по сравнению с сопутствующей ей гистологической нормой был проанализирован уровень экспрессии восьми генов: CD274, LGALS9, PVR, TDO2, IDO1, CD276, CEACAM1 и ADAM17. Экспрессию генов анализировали методом ПЦР в реальном времени. В результате анализа выявили гены с наиболее часто повышенной экспрессией при скПКР: LGALS9, TDO2 и IDO1. Показаны статистически значимые различия уровней экспрессии в изучаемых группах для генов CD274, PVR и CD276 (тест Манна-Уитни, p = <0,001; 0,003; 0,004, соответственно). Полученные данные о молекулярно-генетических механизмах прогрессирования опухоли могут внести вклад в разработку новых терапевтических подходов.

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive histologic subtype of renal tumors. At the time of diagnosis, one-third of patients develop distant metastases. Significant progress in the treatment of metastatic renal cancer has been made with the advent of targeted therapies based on immune checkpoint inhibitors. However, such therapy is not always effective. Therefore, it is relevant to study the molecular mechanisms underlying resistance to therapies that promote renal cancer progression. In this study, tumor samples obtained from patients with metastatic and non-metastatic ccRCC were investigated. The expression levels of eight genes, CD274, LGALS9, PVR, TDO2, IDO1, CD276, CEACAM1 and ADAM17, were analyzed in tumor tissue compared with the corresponding histological normal tissue. Gene expression was analyzed by real-time PCR. LGALS9, TDO2 and IDO1 genes were found to be most frequently upregulated in kidney cancer. Statistically significant differences in expression levels in the studied groups were shown for CD274, PVR and CD276 genes (Mann-Whitney test, p = <0.001; 0.003; 0.004, respectively). Our findings on the molecular genetic level of tumor progression may be useful for the development of new therapeutic treatment regimens.

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