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LncRNAs and EGFRvIII sequestered in TEPs enable blood-based NSCLC diagnosis

Authors Luo CL, Xu ZG, Chen H, Ji J, Wang YH, Hu W, Wang K, Zhang WW, Yuan CH, Wang FB

Received 31 January 2018

Accepted for publication 4 April 2018

Published 8 June 2018 Volume 2018:10 Pages 1449—1459

DOI https://doi.org/10.2147/CMAR.S164227

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Chang-Liang Luo,1,* Zhi-Gao Xu,2,* Hao Chen,2 Jia Ji,1 Yu-Hui Wang,1 Wei Hu,1 Kun Wang,3 Wu-Wen Zhang,1 Chun-Hui Yuan,4 Fu-Bing Wang1

1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China; 2Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China; 3Department of Laboratory Medicine, Hubei Cancer Hospital, Wuhan, China; 4Department of Laboratory Medicine, Wuhan Children’s Hospital, Huazhong University of Science and Technology, Wuhan, China

*These authors contributed equally to this work

Background:
Tissue biopsy-based cancer diagnosis has limitations because of the fact that tumor tissues are in constant evolution and extremely heterogeneous. The current study was aimed to examine whether tumor-educated blood platelets (TEPs) might be a potential all-in-one source for blood-based cancer diagnostics to overcome the limitations of conventional cancer biopsy.
Methods: In the present study, we evaluated the expression pattern of MAGI2 antisense RNA 3 (MAGI2-AS3) and ZNFX1 antisense RNA 1 (ZFAS1) in both plasma and platelets of 101 non-small-cell lung cancer (NSCLC) patients. Receiver operating characteristic (ROC) curve was generated to evaluate their diagnostic potential. In addition, epidermal growth factor receptor (EGFR) mutations were detected in DNA and RNA samples of platelets for companion diagnostics.
Results: Our results showed that the levels of MAGI2-AS3 and ZFAS1 in both plasma and platelets of NSCLC patients were significantly downregulated than those in healthy controls. A positive correlation of long noncoding RNA expression was observed between platelets and plasma (r=0.738 for MAGI2-AS3, r=0.751 for ZFAS1, respectively). By ROC analysis, we found that molecular interrogation of MAGI2-AS3 and ZFAS1 in TEPs and plasma can offer valuable diagnostic performance for NSCLC patients (area under the ROC curve [AUC]MAGI2-AS3=0.853/0.892, and AUCZFAS1=0.780/0.744 for diagnosing adenocarcinoma and squamous cell carcinoma cases from controls, respectively). Clinicopathologic characteristic analysis further revealed that MAGI2-AS3 level significantly correlated with tumor–node–metastasis (TNM) stage (p=0.001 in TEPs, p=0.003 in plasma), lymph-node metastasis (p=0.016 in TEPs, p=0.023 in plasma), and distant metastasis (p=0.045 in TEPs, p=0.045 in plasma), while ZFAS1 level was only correlated with TNM stage (p=0.005 in TEPs, p=0.044 in plasma). Furthermore, EGFRvIII RNA existed in both TEPs and plasma, but EGFR intracellular mutations cannot be detected in DNA of TEPs isolated from NSCLC.
Conclusion: Our data suggested that TEP is a promising source for NSCLC diagnosis and companion diagnostics.

Keywords:
tumor-educated platelets, lncRNA-MAGI2-AS3, lncRNA-ZFAS1, EGFR mutations, NSCLC

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