Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66697610.31857/S0016675824030107DOGQTNГЕНЕТИКА ЧЕЛОВЕКАResearch ArticleExosomal miRNA-146a and miRNA-424 as possible predictors of immune checkpoint inhibitors therapy response in clear cell renal cell carcinomaЭкзосомальные микроРНК-146a и микроРНК-424 как возможные предикторы ответа на терапию ингибиторами иммунных контрольных точек при светлоклеточной почечно-клеточной карциномеAsadullinaD. D.АсадуллинаД. Д.
Russian Federation
dilara.asadullina@yandex.ruGilyazovaI. R.ГилязоваИ. Р.
Russian Federation
gilyasova_irina@mail.ruIvanovaE. A.ИвановаЕ. А.
Russian Federation
dilara.asadullina@yandex.ruIzmailovaS. M.ИзмайловаС. М.
Russian Federation
dilara.asadullina@yandex.ruGilyazovaG. R.ГилязоваГ. Р.
Russian Federation
dilara.asadullina@yandex.ruPavlovV. N.ПавловВ. Н.
Russian Federation
dilara.asadullina@yandex.ruKhusnutdinovaE. K.ХуснутдиноваЭ. К.
Russian Federation
dilara.asadullina@yandex.ruInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукFederal State Budgetary Educational Institution of Higher Education “Bashkir State Medical University” of the Ministry of Health of the Russian FederationБашкирский государственный медицинский университет150320246039410326022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/666976

Clear cell renal cell carcinoma (ccRCC) is a malignant kidney tumor with a poor prognosis and difficult to treat. Despite significant advances in the treatment of ccRCC, immune checkpoint in-hibitors (ICI) still have limited therapeutic efficacy. A growing body of work has demonstrated that exosomal microRNAs are key modulators of tumor signaling and determinants of the tumor microenvironment. Disruption of microRNA regulation may affect ccRCC immunogenicity and response to ICI therapy, making them attractive for use as prognostic molecular genetic bi-omarkers. We evaluated exosomal miRNAs (miRNA-424,-146a,-503, -144) expression levels before and after ICI therapy in plasma samples obtained from 42 ccRCC patients. Expression analysis was performed by real-time PCR method. The results showed that the expression levels of miRNA-424 and miRNA-146a were upregulated after ICI therapy treatment (miRNA-424 = Mean ± SEM 1.202 ± 0.15 and miRNA-146a = 12.22 ± 1.45) compared expression levels before therapy (miRNA-424=Mean±SEM 0.63 ± 0.17; p-value = 0.03 and miRNA-146a = 7.03 ± 0.90; p-value = 0.006). miRNA-424 and miRNA-146a can be used to create a panel of molecular markers for evaluating the effectiveness of immune checkpoint inhibitors therapy. Even though this is very preliminary and requires further studying on a larger sample, it further increases the interest in using microRNAs, as additional ICI therapeutic markers capable of modulating immune tolerance.

Светлоклеточная почечно-клеточная карцинома (скПКК) – злокачественная опухоль почки с плохим прогнозом и трудно поддающаяся лечению. Несмотря на значительные успехи в лечении скПКК, ингибиторы контрольных точек иммунного ответа (ИКТИ) все еще имеют ограниченную терапевтическую эффективность. Все больше работ показывают, что экзосомальные микроРНК являются ключевыми модуляторами опухолевой сигнализации и детерминантами опухолевого микроокружения. Нарушение регуляции микроРНК может влиять на иммуногенность рака и ответ на терапию ИКТИ, что делает их привлекательными для использования в качестве прогностических молекулярно-генетических биомаркеров. Мы оценили уровень экспрессии экзосомальных микроРНК (микроРНК-424, -146а, -503, -144) до и после терапии ИКТИ в образцах плазмы, полученных от 42 больных со скПКК. Анализ экспрессии проводили методом ПЦР в режиме реального времени. Результаты показали, что уровни экспрессии микроРНК-424 и микроРНК-146a были повышены после терапии ИКТИ (микроРНК-424 = Mean ± SEM 1.202 ± 0.15 и микроРНК-146a = 12.22 ± 1.45) по сравнению с уровнями экспрессии до терапии (микроРНК-424 = Mean ± SEM 0.63 ± 0.17; p-value = 0.03 и микроРНК-146a = 7.03 ± 0.90; p-value = 0.006). МикроРНК-424 и микроРНК-146a могут быть использованы для создания панели молекулярных маркеров для оценки эффективности терапии ингибиторами иммунных контрольных точек. Несмотря на то что полученные данные являются весьма предварительными и требуют дальнейшего изучения на более крупной выборке, они еще больше повышают интерес к использованию микроРНК в качестве дополнительных маркеров терапии ИКТИ, способных модулировать иммунную толерантность.

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