TY - JOUR

T1 - Exosomal miRNA-146a is downregulated in clear cell renal cell carcinoma patients with severe immune-related adverse events

AU - Иванова, Елизавета Алексеевна

AU - Асадуллина, Дилара Динаровна

AU - Рахимов, Радмир Радимович

AU - Измайлов, Адель Альбертович

AU - Гилязова, Гульшат Руслановна

AU - Измайлов, Альберт Аделевич

AU - Галимов, Шамиль Нуриманович

AU - Павлов, Валентин Николаевич

AU - Хуснутдинова, Эльза Камилевна

AU - Гилязова, Ирина Ришатовна

N1 - Publisher Copyright: © 2022 The Authors

PY - 2022/9

Y1 - 2022/9

N2 - 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 CC genotype and C allele carriers had higher risk of developing severe irAEs (p = 0.03, OR = 6.12; p = 0.01, OR = 2.42, respectively) compare with GG and GC 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.

AB - 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 CC genotype and C allele carriers had higher risk of developing severe irAEs (p = 0.03, OR = 6.12; p = 0.01, OR = 2.42, respectively) compare with GG and GC 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.

KW - Exosomal miRNAs

KW - Gene expression

KW - Gene polymorphism

KW - Immune-related adverse events

KW - Nivolumab

KW - Renal cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85133520611&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/f73022ec-0aa3-3425-b9df-2dafe0750702/

U2 - 10.1016/j.ncrna.2022.06.004

DO - 10.1016/j.ncrna.2022.06.004

M3 - Article

C2 - 35846077

VL - 7

SP - 159

EP - 163

JO - Non-coding RNA Research

JF - Non-coding RNA Research

SN - 2468-0540

IS - 3

ER -