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Exosomal MicroRNA Levels Associated with Immune Checkpoint Inhibitor Therapy in Clear Cell Renal Cell Carcinoma
Elizaveta Ivanova1, Dilara Asadullina1, Gulshat Gilyazova2
1Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, 450054 Ufa, Russia.
Abstract:
Immunotherapy with immune checkpoint inhibitors (ICIs) has shown high efficiency in clear cell renal cell carcinoma (ccRCC) treatment. However, the response to therapy among patients varies greatly. Modern studies demonstrate the high potential of exosomal miRNAs as diagnostic and prognostic markers in oncopathology. This study aimed to evaluate exosomal miRNA expression profiles of miRNAs-144, -146a, -149, -126, and -155 in patients with clear cell renal cell carcinoma treated with immune checkpoint inhibitors. The study included 35 patients whose venous blood samples were taken before and after ICI therapy. Expression analysis was performed using real-time quantitative PCR. It was demonstrated that the level of microRNA-146a increased after therapy (median(IQR) 12.92(4.06-18.90)) compared with the level before it (median(IQR) 7.15(1.90-10.50); p-value = 0.006). On the contrary, microRNA-126 was reduced after therapy with immune checkpoint inhibitors (median(IQR) 0.85(0.55-1.03) vs. 0.48(0.15-0.68) before and after therapy, respectively; p-value = 0.0001). In addition, miRNA-146a expression was shown to be reduced in patients with a higher grade of immune-related adverse events (p-value = 0.020). The AUC value for the miRNA-146a and miRNA-126 combination was 0.752 (95% CI 0.585-0.918), with the sensitivity at 64.3% and the specificity at 78.9%. Thus, while it can be assumed that miRNA-146a and miRNA-126 can be used as predictors for ICI therapy effectiveness, additional in-depth studies are required.
Insights
Exosomal microRNA-146a and microRNA-126 levels change after immune checkpoint inhibitor (ICI) therapy for clear cell renal cell carcinoma (ccRCC). These microRNAs may predict treatment effectiveness and adverse events in ccRCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICIs) are effective in clear cell renal cell carcinoma (ccRCC) but patient responses vary.
- Exosomal microRNAs (miRNAs) show potential as diagnostic and prognostic markers in cancer.
- Understanding biomarkers for ICI therapy response is crucial for personalized treatment in ccRCC.
Purpose of the Study:
- To evaluate exosomal miRNA expression profiles (miRNA-144, -146a, -149, -126, -155) in ccRCC patients undergoing ICI therapy.
- To investigate the association of these exosomal miRNAs with treatment response and immune-related adverse events (irAEs).
- To assess the potential of exosomal miRNAs as predictive biomarkers for ICI therapy in ccRCC.
Main Methods:
- Analysis of exosomal miRNA expression (miRNA-146a, -126) in 35 ccRCC patients before and after ICI therapy.
- Venous blood samples were collected for expression analysis using real-time quantitative PCR.
- Statistical analysis included comparisons of miRNA levels and correlation with irAEs and treatment outcomes.
Main Results:
- Exosomal microRNA-146a levels significantly increased after ICI therapy (p=0.006).
- Exosomal microRNA-126 levels significantly decreased after ICI therapy (p=0.0001).
- Reduced miRNA-146a expression correlated with higher-grade immune-related adverse events (p=0.020).
- A combination of miRNA-146a and miRNA-126 showed an AUC of 0.752 for predicting therapy effectiveness.
Conclusions:
- Exosomal miRNA-146a and miRNA-126 levels dynamically change during ICI therapy in ccRCC patients.
- These miRNAs show potential as predictive biomarkers for ICI therapy effectiveness and irAEs in ccRCC.
- Further research is warranted to validate these findings and explore their clinical utility.
