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热消融和经动脉化疗栓塞术的特点是循环 microRNAs 动力学的变化。

Thermal Ablation and Transarterial Chemoembolization are Characterized by Changing Dynamics of Circulating MicroRNAs.

机构信息

Department of Radiology and Nuclear Medicine, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic.

Masaryk University, Central European Institute of Technology, Brno, Czech Republic.

出版信息

J Vasc Interv Radiol. 2021 Mar;32(3):403-411. doi: 10.1016/j.jvir.2020.10.024. Epub 2021 Jan 23.

Abstract

PURPOSE

To determine whether the levels of circulating microRNAs (miRNAs) are altered in patients undergoing thermal ablation and chemoembolization and whether these changes are predictive of a clinical outcome.

MATERIAL AND METHODS

This prospective study consisted of 43 patients diagnosed with hepatocellular carcinoma (n = 15) and intrahepatic colorectal cancer metastases (n = 28) treated with thermal ablation (n = 23; radiofrequency [n = 6] or microwave [n = 19]), chemoembolization using drug-eluting embolics (n = 18), or both (n = 2). Four blood samples (immediately before the intervention and 60-90 minutes, 24 hours, and 7 days after the intervention) were taken to measure the plasma concentrations of miRNAs related to hypoxia (miR-21 and miR-210), liver injury (miR-122), epithelial-mesenchymal transition (miR-200a), and apoptosis (miR-34a) using miRNA-specific TaqMan assays and quantitative real-time polymerase chain reaction. Tumor burden and treatment response at 3 months were evaluated using the modified response evaluation criteria in solid tumors. The miRNA results were compared with clinical outcomes (Mann-Whitney U test, Wilcoxon matched-pair test).

RESULTS

Dynamic changes in the circulating miRNA levels were observed following both the interventions. For thermal ablation, significant increases in miR-21, miR-210, miR-122, miR-200a, and miR-34a concentrations peaked 60-90 minutes after the intervention (P < .01). However, for transarterial chemoembolization, maximum increases in the miRNA concentrations were observed at 24 hours after the intervention for miR-21, miR-210, miR-122, miR-200a, and miR-34a (P < .05). The increased concentrations of the circulating miRNAs were followed by a subsequent decline to baseline by 7 days. For the thermal ablation (but not chemoembolization) patients, elevations in the miR-210 and miR-200a levels were associated with early progressive disease at 3 months (P = .040 and P = .012, respectively).

CONCLUSIONS

Increased but dynamic levels of circulating miRNAs are present following interventional oncologic procedures and may prove useful as biomarkers for the monitoring of clinical outcomes.

摘要

目的

确定循环 microRNA(miRNA)水平在接受热消融和化疗栓塞的患者中是否发生改变,以及这些变化是否具有预测临床结果的能力。

材料与方法

本前瞻性研究纳入了 43 名接受热消融(射频消融 6 例,微波消融 19 例)、载药微球化疗栓塞(18 例)或两者联合(2 例)治疗的肝细胞癌(n=15)和肝内结直肠癌转移患者(n=28)。分别于干预前即刻及干预后 60-90 分钟、24 小时和 7 天时采集 4 份血样,采用 miRNA 特异性 TaqMan 分析和实时定量聚合酶链反应检测与缺氧(miR-21 和 miR-210)、肝损伤(miR-122)、上皮间质转化(miR-200a)和细胞凋亡(miR-34a)相关的血浆 miRNA 浓度。采用改良实体瘤疗效评价标准评价 3 个月时的肿瘤负荷和治疗反应。采用 Mann-Whitney U 检验和 Wilcoxon 配对检验比较 miRNA 结果与临床结局。

结果

两种干预后均观察到循环 miRNA 水平的动态变化。热消融后,miR-21、miR-210、miR-122、miR-200a 和 miR-34a 浓度在干预后 60-90 分钟时显著升高(P<0.01)。然而,经动脉化疗栓塞后,miR-21、miR-210、miR-122、miR-200a 和 miR-34a 的 miRNA 浓度在干预后 24 小时时达到最大值(P<0.05)。这些循环 miRNA 浓度升高后,7 天内降至基线。对于热消融(而非化疗栓塞)患者,miR-210 和 miR-200a 水平升高与 3 个月时的早期进展性疾病相关(P=0.040 和 P=0.012)。

结论

介入性肿瘤治疗后存在循环 miRNA 水平升高,但呈动态变化,可能可用作监测临床结果的生物标志物。

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