Circulating exosomal microRNAs as biomarkers of colon cancer.
Circulating exosomal microRNAs as biomarkers of colon cancer.
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DOI：
10.1371/journal.pone.0092921
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tsuchiya N
中科院分区：
文献类型：
--
作者：
Ogata-Kawata H;Izumiya M;Kurioka D;Honma Y;Yamada Y;Furuta K;Gunji T;Ohta H;Okamoto H;Sonoda H;Watanabe M;Nakagama H;Yokota J;Kohno T;Tsuchiya N
外泌体microRNA（miRNAs）作为潜在的癌症诊断生物标志物已经引起了人们的极大兴趣。本研究的目的是表征血清外泌体的miRNA谱，并鉴定在结直肠癌（CRC）中改变的那些。为了评估它们作为诊断生物标志物的用途，检查了特异性外泌体miRNA水平与患者病理变化（包括疾病阶段和肿瘤切除）之间的关系。对来自88名原发性CRC患者和11名健康对照的血清样品的富含外泌体的组分中的miRNA进行微阵列分析。还将5种结肠癌细胞系的培养基中的miRNA表达水平与正常结肠来源的细胞系的培养基中的miRNA表达水平进行了比较。使用来自肿瘤切除术后患者的29个配对样本验证CRC和对照样本集之间差异表达的miRNA的表达谱。采用受试者操作特征分析法，对所选miRNA作为CRC生物标志物的敏感性进行评估，并与已知肿瘤标志物（CA 19 -9和CEA）进行比较。所选miRNA的表达水平也通过13名CRC患者的独立组的定量实时RT-PCR分析来验证。7种miRNA（let-7a、miR-1229、miR-1246、miR-150、miR-21、miR-223和miR-23 a）的血清外泌体水平在原发性CRC患者中显著高于健康对照，即使是那些患有早期疾病的患者，并且在手术切除肿瘤后显著下调。结肠癌细胞系分泌的这些miRNA水平也显著高于正常结肠来源的细胞系。通过受试者操作特征分析证实了七种选择的外泌体miRNA的高灵敏度。外泌体miRNA特征似乎反映了CRC患者的病理变化，并且几种miRNA是用于该疾病的非侵入性诊断的有希望的生物标志物。
Exosomal microRNAs (miRNAs) have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC). To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined. Microarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA) using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients. The serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a) were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis. Exosomal miRNA signatures appear to mirror pathological changes of CRC patients and several miRNAs are promising biomarkers for non-invasive diagnosis of the disease.
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通讯作者：
Piiper A