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

• Published in: Cancer management and research 2018-01, Vol.10, p.1449-1459
• Main Authors: Luo, Chang-Liang, Xu, Zhi-Gao, Chen, Hao, Ji, Jia, Wang, Yu-Hui, Hu, Wei, Wang, Kun, Zhang, Wu-Wen, Yuan, Chun-Hui, Wang, Fu-Bing
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Analysis; Antisense RNA; Blood platelets; Cancer; Cancer diagnosis; Cancer metastasis; Cancer patients; Cancer research; Carcinoma; DNA; DNA methylation; EGFR mutations; Epidermal growth factors; Health aspects; Kinases; Laboratories; lncRNA-MAGI2-AS3; lncRNA-ZFAS1; Lung cancer; Mutation; Non-small cell lung cancer; NSCLC; Original Research; RNA; Squamous cell carcinoma; Tumor-educated platelets; Tumors
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S164227

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. In the present study, we evaluated the expression pattern of MAGI2 antisense RNA 3 ( ) and ZNFX1 antisense RNA 1 ( ) 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 ( ) mutations were detected in DNA and RNA samples of platelets for companion diagnostics. Our results showed that the levels of and 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 ( =0.738 for , =0.751 for , 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] = 0.853/0.892, and AUC =0.780/0.744 for diagnosing adenocarcinoma and squamous cell carcinoma cases from controls, respectively). Clinicopathologic characteristic analysis further revealed that level significantly correlated with tumor-node-metastasis (TNM) stage ( =0.001 in TEPs, =0.003 in plasma), lymph-node metastasis ( =0.016 in TEPs, =0.023 in plasma), and distant metastasis ( =0.045 in TEPs, =0.045 in plasma), while level was only correlated with TNM stage ( =0.005 in TEPs, =0.044 in plasma). Furthermore, RNA existed in both TEPs and plasma, but intracellular mutations cannot be detected in DNA of TEPs isolated from NSCLC. Our data suggested that TEP is a promising source for NSCLC diagnosis and companion diagnostics.