Urinary-derived extracellular vesicle microRNAs as non‐invasive diagnostic biomarkers for early-stage renal cell carcinoma

小RNA 阶段(地层学) 肾细胞癌 癌症 泌尿系统 肾癌 医学 肿瘤科 细胞外小泡 下调和上调 内科学 癌症研究 生物信息学 生物 基因 遗传学 细胞生物学 古生物学
作者
Yu Zhang,Yuanyuan Zhu,Yang Chen,Lele Zhang,Rong Wang,Xiaoyu Ding,Huizi Zhang,Chen‐Yu Zhang,Chen‐Yu Zhang,Wanjian Gu,Cheng Wang,Junjun Wang
出处
期刊:Clinica Chimica Acta [Elsevier BV]
卷期号:552: 117672-117672 被引量:5
标识
DOI:10.1016/j.cca.2023.117672
摘要

The potential of urinary-derived extracellular vesicle (uEV) microRNAs (miRNAs) as noninvasive molecular biomarkers for identifying early-stage renal cell carcinoma (RCC) patients is rarely explored. The present study aims to explore the possibility of uEV miRNAs as novel molecular biomarkers for distinguishing early-stage RCC.uEVs were extracted by ExoQuick-TC™ kit and miRNA concentrations were measured by RT-qPCR. ROC curves and bioinformatics analysis were employed to predict the diagnostic efficacy and regulatory mechanisms of dysregulated miRNAs.Through a multiphase case-control study on uEV miRNAs screening, training, and validation in RCC cells (ACHN, Caki-1) and control cells (HK-2) and in uEVs of 125 RCC patients and 128 age- and sex-matched controls, we successfully identified four uEVs miRNAs (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) were significantly and stably upregulated in RCC in vitro and in vivo. When adjusted with estimated glomerular filtration rate (eGFR), the AUC of the three-uEV miRNA panel (miR-135b-5p, miR-200c-3p, and miR-203a-3p) was 0.785 (95 % CI = 0.729-0.842, P < 0.0001) for discriminating RCC patients from controls. Notably, this panel exhibited similar performance in distinguishing early-stage (stage Ⅰ) RCC patients, with an AUC of 0.786 (95 %CI = 0.727-0.844, P < 0.0001). Bioinformatics analysis predicted that candidate miRNAs were involved in cancer progressing.Our study identified a four uEV miRNAs panel (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) may serve as an auxiliary noninvasive indication of early-stage RCC.
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