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Exosomal miRNA-146a and miRNA-424 as Possible Predictors of Immune Checkpoint Inhibitors Therapy Response in Clear Cell Renal Cell Carcinoma

  • HUMAN GENETICS
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Abstract

Clear cell renal cell carcinoma (ccRCC) is a malignant kidney tumour with a poor prognosis and difficult to treat. Despite significant advances in the treatment of ccRCC, immune checkpoint inhibitors (ICI) still have limited therapeutic efficacy. A growing number of investigations has demonstrated that exosomal miRNAs are key modulators of tumour signaling and determinants of the tumour microenvironment. Disruption of miRNA regulation may affect ccRCC immunogenicity and response to ICI therapy, making them attractive for use as prognostic molecular genetic biomarkers. 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 using 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 the results are preliminary and requires further studying on a larger cohorts, it further increases the interest in using miRNAs, as additional ICI therapeutic markers capable of modulating immune tolerance.

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Funding

The study was supported by the Russian Science Foundation grant no. 23-25-00392, available at https://rscf.ru/project/23-25-00392/.

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Authors and Affiliations

  1. Institute of Biochemistry and Genetics—Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, 450054, Ufa, Russia

    D. D. Asadullina, I. R. Gilyazova, E. A. Ivanova & E. K. Khusnutdinova

  2. Bashkir State Medical University of the Ministry of Health of the Russian Federation, 450008, Ufa, Russia

    D. D. Asadullina, I. R. Gilyazova, S. M. Izmailova, G. R. Gilyazova, V. N. Pavlov & E. K. Khusnutdinova

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  1. D. D. Asadullina
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  2. I. R. Gilyazova
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  3. E. A. Ivanova
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  4. S. M. Izmailova
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  5. G. R. Gilyazova
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Correspondence to D. D. Asadullina or I. R. Gilyazova.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The study was approved by the Ethics Committee of the Institute of Biochemistry and Genetics—Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, protocol No. 11 dated October 27, 2014. Informed consent was obtained from all individual participants involved in the study. All participants were adults.

Written informed consent form for the collection of biological samples and molecular-genetic analysis was obtained from each patient.

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The authors of this work declare that they have no conflicts of interest.

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Asadullina, D.D., Gilyazova, I.R., Ivanova, E.A. et al. Exosomal miRNA-146a and miRNA-424 as Possible Predictors of Immune Checkpoint Inhibitors Therapy Response in Clear Cell Renal Cell Carcinoma. Russ J Genet 60, 367–374 (2024). https://doi.org/10.1134/S1022795424030025

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