Exosomal MicroRNA Levels Associated with Immune Checkpoint Inhibitor Therapy in Clear Cell Renal Cell Carcinoma.

Exosomal MicroRNA Levels Associated with Immune Checkpoint Inhibitor Therapy in Clear Cell Renal Cell Carcinoma.
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透明细胞肾细胞癌中与免疫检查点抑制剂治疗相关的外泌体 MicroRNA 水平。

DOI:
10.3390/biomedicines11030801
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发表时间:
2023-03-06
期刊:
影响因子:
4.7
通讯作者:
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中科院分区:
工程技术3区
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免疫检查点抑制剂(ICIs)的免疫疗法在透明细胞肾细胞癌(ccRCC)治疗中显示出高效。然而,患者对治疗的反应差异很大。现代研究证明外泌体 miRNA 作为肿瘤病理学诊断和预后标志物的巨大潜力。本研究旨在评估接受免疫检查点抑制剂治疗的透明细胞肾细胞癌患者中 miRNA-144、-146a、-149、-126 和 -155 的外泌体 miRNA 表达谱。该研究纳入了 35 名患者,他们在 ICI 治疗前后采集了静脉血样本。使用实时定量PCR进行表达分析。研究表明,治疗后 microRNA-146a 水平较治疗前水平(中位(IQR)7.15(1.90-10.50);p 值 = 0.006)有所增加(中位(IQR)12.92(4.06-18.90))。相反,免疫检查点抑制剂治疗后 microRNA-126 减少(治疗前后中位数 (IQR) 分别为 0.85(0.55–1.03) vs. 0.48(0.15–0.68);p 值 = 0.0001)。此外,在免疫相关不良事件级别较高的患者中,miRNA-146a 表达降低(p 值 = 0.020)。 miRNA-146a 和 miRNA-126 组合的 AUC 值为 0.752 (95% CI 0.585–0.918),敏感性为 64.3%,特异性为 78.9%。因此,虽然可以假设 miRNA-146a 和 miRNA-126 可用作 ICI 治疗有效性的预测因子,但仍需要进行额外的深入研究。
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.
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