Evaluation of Tumor-Derived Exosomal miRNA as Potential Diagnostic Biomarkers for Early-Stage Non–Small Cell Lung Cancer Using Next-Generation Sequencing

Xiance Jin; Yanfan Chen; Hanbin Chen; Shaoran Fei; Didi Chen; Xiaona Cai; Linger Liu; Baochai Lin; Huafang Su; Lihao Zhao; Meng Su; Huanle Pan; Lanxiao Shen; Deyao Xie; Congying Xie

doi:10.1158/1078-0432.ccr-17-0577

journal article Aug 31, 2017

Evaluation of Tumor-Derived Exosomal miRNA as Potential Diagnostic Biomarkers for Early-Stage Non–Small Cell Lung Cancer Using Next-Generation Sequencing

Xiance Jin Yanfan Chen Hanbin Chen Shaoran Fei Didi Chen Xiaona Cai Linger Liu Baochai Lin Huafang Su Lihao Zhao

Meng Su

Huanle Pan Lanxiao Shen Deyao Xie Congying Xie

Clinical Cancer Research Vol. 23 No. 17 pp. 5311-5319 · American Association for Cancer Research (AACR)

View at Publisher Save 10.1158/1078-0432.ccr-17-0577

Abstract

Abstract
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. Clin Cancer Res; 23(17); 5311–9. ©2017 AACR.

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Details

Published: Aug 31, 2017
Vol/Issue: 23(17)
Pages: 5311-5319

Authors

X

Xiance Jin