Ivanova E, Asadullina D, Rakhimov R, Izmailov A, Izmailov Al, Gilyazova G, Galimov Sh, Pavlov V, Khusnutdinova E, Gilyazova I
Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, 450054, Russian Federation.
St.Petersburg State University, Russian Federation.
Noncoding RNA Res. 2022 Jul 1;7(3):159-163. doi: 10.1016/j.ncrna.2022.06.004. eCollection 2022 Sep.
Here we report the results of the pilot project of exosomal miRNA expression levels in clear cell renal cell carcinoma (ccRCC) patients with different clinical response to ICIs (nivolumab) and treatment related toxicity. Immune-related adverse events (irAEs) are a major cause of immune checkpoint inhibitors cancellation and therapy failure. Modern studies demonstrate evidence that exosomes are of great importance in the formation of tumor resistance to ICIs drugs and therapy. We performed exosomal miRNA-146a expression analysis using qPCR on 86 ccRCC patients and revealed a statistically significant (p = 0.01) decreased expression level in ccRCC patients with CTCAE grade 3-4 (M±SEM 1.71 ± 0.13) compared to CTCAE grade 0-2 group (M±SEM 2.30 ± 0.24). The expression levels of miRNA-126, miRNA-218 and miRNA-410 did not show statistically significant differences in the comparison groups (p > 0.05). Association analysis of rs2910164 in the miRNA-146a gene demonstrated that genotype and allele carriers had higher risk of developing severe irAEs (p = 0.03, OR = 6.12; p = 0.01, OR = 2.42, respectively) compare with and carriers. That is the first attempt to identify biomarkers of ICIs treatment efficacy for ccRCC in the Volga-Ural region based on exosomal miRNAs analysis.
在此，我们报告了一项关于透明细胞肾细胞癌（ccRCC）患者外泌体miRNA表达水平的试点项目结果，这些患者对免疫检查点抑制剂（纳武单抗）有不同的临床反应以及治疗相关毒性。免疫相关不良事件（irAEs）是免疫检查点抑制剂停药和治疗失败的主要原因。现代研究表明，有证据显示外泌体在肿瘤对ICI药物和治疗产生抗性的形成过程中具有重要作用。我们对86例ccRCC患者进行了qPCR外泌体miRNA - 146a表达分析，结果显示，与CTCAE 0 - 2级组（M±SEM 2.30±0.24）相比，CTCAE 3 - 4级ccRCC患者的表达水平有统计学显著下降（p = 0.01）（M±SEM 1.71±0.13）。miRNA - 126、miRNA - 218和miRNA - 410的表达水平在比较组中未显示出统计学显著差异（p>0.05）。miRNA - 146a基因中rs2910164的关联分析表明，与 和 携带者相比， 基因型和 等位基因携带者发生严重irAEs的风险更高（分别为p = 0.03，OR = 6.12；p = 0.01，OR = 2.42）。这是基于外泌体miRNA分析在伏尔加 - 乌拉尔地区首次尝试鉴定ccRCC的ICI治疗疗效生物标志物。
