Abstract
Abstract Objective: The lack of useful biomarker contributes to the increased morbidity and mortality of non-small cell lung cancer (NSCLC) partly. However, biomarkers in blood have become increasingly appreciated in diagnosis of NSCLC. This study, we aimed to identify serum miRNAs for diagnosing NSCLC. Methods: Microarray were used to detect 2549 miRNAs in serum from NSCLC patients (n=10) and healthy individuals (n=10) and gain differentially expressed miRNAs. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay were applied to validate the expression of selected miRNAs in validation set consisting of sera from 60 participants. Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy of the chosen miRNAs. Tissue expression of the selected miRNA was analyzed based on TCGA database. Subsequently, the target gene of the miRNAs were predicted by TargetScan and Gene ontology (GO) and KEGG pathway enrichment analysis tested by R (clusterProfiler package). The effect of miR-4687-3p on proliferation, invasion, and metastasis of lung cancer cells were investigated through CCK-8 and Transwell assay. Results: We identified serum miR-4687-3p that provided a high diagnostic accuracy of NSCLC (AUC=0.69, 95%CI: 0.543-0.815) in validation data set. According to TCGA database, we also found that the tissue miR-4687-3p level were significantly higher in NSCLC tissues than normal tissues (p<0.05). GO and KEGG pathway enrichment analysis showed that postsynaptic specialization and TGF-β signaling pathway were significantly enriched. Up-regulated miR-4687-3p by miR-4687-3p mimic could promote the proliferation, invasion, and metastasis of the NSCLC cells, compared with mimic negative control. Meanwhile, applying miR-4687-3p inhibitor could suppressed the proliferation, invasion, and metastasis of the NSCLC cells. Conclusion: Our study on the first reported that serum miR-4687-3p levels may have clinical potentials as a novel non-invasive diagnostic biomarker for NSCLC patients. Key words: NSCLC, miR-4687-3p, microarray, bioinformatics, biomarker Citation Format: Man Liu, Jun Ouyang, Qiufang Si, Yulin Wang, Ting Yang, Xue Zhang, Di Jiang, Jianying Zhang, Liping Dai. Serum miR-4687-3p as the diagnostic biomarker for NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3126.
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