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Seven-microRNA panel for lung adenocarcinoma early diagnosis in patients presenting with ground-glass nodules

Authors He Y, Yang Y, Kuang P, Ren S, Rozeboom L, Rivard CJ, Li X, Zhou C, Hirsch FR

Received 12 September 2017

Accepted for publication 28 October 2017

Published 13 December 2017 Volume 2017:10 Pages 5915—5926

DOI https://doi.org/10.2147/OTT.S151432

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Samir Farghaly


Yayi He,1,2,* Yang Yang,3,* Peng Kuang,1 Shengxiang Ren,1 Leslie Rozeboom,2 Christopher J Rivard,2 Xuefei Li,4 Caicun Zhou,1 Fred R Hirsch2

1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 3Department of Surgery, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, 4Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Background: MicroRNA (miRNA) expression is correlated with tumor histology, differentiation, invasiveness and treatment outcome. We aimed to identify miRNAs whose differential expression might enable early diagnosis of lung adenocarcinoma in patients presenting with ground-glass nodules (GGNs).
Methods: To identify potential miRNAs of interest, we analyzed the miRNA expression profile of tumor and adjacent non-para-tumor tissue in three participants by next-generation sequencing (NGS). We then assessed the expression levels of the miRNAs of interest in 73 lung adenocarcinomas presenting with GGNs with matched adjacent non-tumor tissue by quantitative real-time polymerase chain reaction (qRT-PCR). We also detected the miRNA panel in 66 lung benign diseases and 66 lung adenocarcinomas presenting with GGN lesion tissues by qRT-PCR. Target genes of our selected miRNA panel were predicted using Miranda with default parameters.
Results: Twenty-three miRNAs showed differential expression between tumor and adjacent non-tumor tissue by NGS. Five miRNAs exhibited higher expression in tumor tissue compared to adjacent non-tumor tissue (P<0.05); 18 miRNAs demonstrated lower expression in tumor tissue versus adjacent non-tumor tissue (P<0.05). When qRT-PCR was performed for the 23 miRNAs identified by NGS in the pilot stage, seven were found to have statistically significant expression in tumor versus adjacent non-tumor tissue (P<0.05). The sensitivity and specificity of seven-miRNA panel were 86.4% and 60.6%, respectively.
Conclusion: The predicted targets of our miRNAs of interest are frequently associated with cancer signaling pathways. We developed a miRNA panel that could potentially predict the presence of lung adenocarcinoma in patients presenting with GGNs.

Keywords: microRNA, miRNA, ground-glass nodules, GGNs, next-generation sequencing, NGS, lung adenocarcinoma, early diagnosis

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