MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma.
MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma.
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DOI：
10.18632/oncotarget.14969
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发表时间：
2017-04-11
期刊：
影响因子：
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通讯作者：
Nonomura N
中科院分区：
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作者：
Matsuzaki K;Fujita K;Jingushi K;Kawashima A;Ujike T;Nagahara A;Ueda Y;Tanigawa G;Yoshioka I;Ueda K;Hanayama R;Uemura M;Miyagawa Y;Tsujikawa K;Nonomura N
胞外囊泡是含有蛋白质、信使RNA和微小RNA的脂质双层囊泡。癌细胞衍生的细胞外囊泡可能是诊断和治疗靶点。我们从尿路上皮癌患者和对照组的尿液中提取细胞外囊泡，以鉴定尿液细胞外囊泡中的癌症特异性microRNA作为新的生物标志物。分析了从6名尿路上皮癌患者和3名健康志愿者中提取的尿细胞外囊泡的microRNA。我们在60个尿细胞外囊泡样本的独立队列中验证了候选microRNA。为了标准化细胞外囊泡中的microRNA表达水平，我们检查了细胞外囊泡中的以下内容：蛋白质浓度、CD 9强度、完整miRNA的量、RNA U6 B小核表达和与通过NanoSight™系统测量的提取的细胞外囊泡的计数相关的原始尿液的肌酸酐浓度。从微阵列结果中鉴定出5种在尿路上皮癌患者的尿细胞外囊泡中过表达的microRNA。原始尿液肌酐浓度与细胞外囊泡的颗粒计数相关性最大，表明肌酐可能是使microRNA表达正常化的新工具。miR-21- 5 p是尿细胞外囊泡中最有效的生物标志物（灵敏度，75.0%;特异性，95.8%），并且在尿细胞学阴性的尿路上皮癌患者的尿细胞外囊泡中也过表达。尿细胞学阴性亚组的敏感性为75.0%，特异性为95.8%。尿细胞外小泡中的miR-21- 5 p可能是尿路上皮癌的一个新的生物标志物，尤其适用于尿细胞学阴性的尿路上皮癌患者。
Extracellular vesicles are lipid bilayer vesicles containing protein, messengerRNA and microRNA. Cancer cell-derived extracellular vesicles may be diagnostic and therapeutic targets. We extracted extracellular vesicles from urine of urothelial carcinoma patients and the control group to identify cancer-specific microRNAs in urinary extracellular vesicles as new biomarkers. microRNA from urinary extracellular vesicles extracted from 6 urothelial carcinoma patients and 3 healthy volunteers was analyzed. We verified candidate microRNAs in an independent cohort of 60 urinary extracellular vesicles samples. To normalize the microRNA expression level in extracellular vesicles, we examined the following in extracellular vesicles: protein concentration, CD9 intensity, amounts of whole miRNAs, RNA U6B small nuclear expression and the creatinine concentration of original urine correlating with the counts of extracted extracellular vesicles measured by the NanoSight™ system. From the microarray results 5 microRNAs overexpressed in urinary extracellular vesicles of urothelial carcinoma patients were identified. Creatinine concentration of original urine correlated most with particle counts of extracellular vesicles, indicating that creatinine could be a new tool for normalizing microRNA expression. MiR-21-5p was the most potent biomarker in urinary extracellular vesicles (sensitivity, 75.0%; specificity, 95.8%) and was also overexpressed in urinary extracellular vesicles from urothelial carcinoma patients with negative urine cytology. For the subgroup with negative urine cytology, the sensitivity was 75.0% and specificity was 95.8%. MiR-21-5p in urinary extracellular vesicles could be a new biomarker of urothelial carcinoma, especially for urothelial carcinoma patients with negative urine cytology.