Evaluation of Tumor-Derived Exosomal miRNA as Potential Diagnostic Biomarkers for Early-Stage Non-Small Cell Lung Cancer Using Next-Generation Sequencing
Evaluation of Tumor-Derived Exosomal miRNA as Potential Diagnostic Biomarkers for Early-Stage Non-Small Cell Lung Cancer Using Next-Generation Sequencing
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DOI：
10.1158/1078-0432.ccr-17-0577
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发表时间：
2017-09-01
影响因子：
11.5
通讯作者：
Xie, Congying
中科院分区：
文献类型：
--
作者：
Jin, Xiance;Chen, Yanfan;Xie, Congying
目的：为了鉴定能够区分腺癌和鳞状细胞癌（SCC）的肿瘤来源的外泌体生物标志物作为非小细胞肺癌（NSCLC）早期诊断的非侵入性方法，实验设计：从早期NSCLC患者的血浆中分离肿瘤来源的外泌体。使用miRNA-seq对46名I期NSCLC患者和42名健康个体进行外泌体miRNA分析，以鉴定和验证腺癌和SCC特异性miRNA。结果：与健康志愿者相比，腺癌和SCC患者中分别有11和6个miRNAs表达显著增高，13和8个miRNAs表达较低。验证了不同的腺癌特异性和SCC特异性外泌体miRNA。miRNA-seq数据的可靠性用几种已证实的NSCLC和其他癌症的诊断潜力miRNA进行了验证，如先前研究中报道的let-7、miR-21、miR-24和miR-486。结果表明，miR-181- 5 p、miR-30 a-3 p、miR-30 e-3 p和miR-361- 5 p是腺癌特异性的，而miR-10 b-5 p、miR-15 b-5 p和miR-320 b是SCC特异性的。使用AUC值0.899、0.936和0.911分别评估三种组合miRNA组检测NSCLC、腺癌和SCC的诊断准确性。肿瘤来源的外泌体miRNA，腺癌特异性miR-181- 5 p、miR-30 a-3 p、miR-30 e-3 p和miR-361- 5 p，以及SCC特异性miR-10 b-5 p、miR-15 b-5 p，和miR-320 b，验证其诊断准确性。这些miRNAs可能是开发用于早期NSCLC诊断的高度敏感、非侵入性生物标志物的有希望和有效的候选者。(C)2017年AACR。
Purpose: To identify tumor-derived exosomal biomarkers that are able to discriminate between adenocarcinoma and squamous cell carcinoma (SCC) as a noninvasive method in the early diagnosis of non-small cell lung cancer (NSCLC).Experimental Design: Tumor-derived exosomes from the plasma of early-stage NSCLC patients were isolated. Exosomal miRNA profiling of 46 stage I NSCLC patients and 42 healthy individuals was performed using miRNA-seq to identify and validate adenocarcinoma- and SCC-specific miRNAs. The diagnostic accuracy of select miRNAs was tested further with an additional 60 individuals.Results: There were 11 and 6 miRNAs expressed at remarkably higher levels, 13 and 8 miRNAs expressed at lower levels in adenocarcinoma and SCC patients, respectively, compared with healthy volunteers. Distinct adenocarcinoma- and SCC-specific exosomal miRNAs were validated. The reliability of miRNA-seq data was verified with several demonstrated diagnostic potential miRNAs for NSCLC and other carcinomas, as reported in previous studies, such as let-7, miR-21, miR-24, and miR-486. The results indicated that miR-181-5p, miR-30a-3p, miR-30e-3p, and miR-361-5p were adenocarcinoma-specific, and miR-10b-5p, miR-15b-5p, and miR-320b were SCC-specific. The diagnostic accuracy of three combination miRNA panels was evaluated using an AUC value of 0.899, 0.936, and 0.911 for detecting NSCLC, adenocarcinoma, and SCC, respectively.Conclusions: Tumor-derived exosomal miRNAs, adenocarcinoma-specific miR-181-5p, miR-30a-3p, miR-30e-3p and miR-361-5p, and SCC-specific miR-10b-5p, miR-15b-5p, and miR-320b were observed by next-generation sequencing, and their diagnostic accuracy were verified. These miRNAs may be promising and effective candidates in the development of highly sensitive, noninvasive biomarkers for early NSCLC diagnosis. (C) 2017 AACR.