| Summary: | Yining Wu,1,* Jia Wei,1,* Wei Zhang,1,2 Mengxiao Xie,1,2 Xueying Wang,1 Jian Xu1,2 1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2National Key Clinical Department of Laboratory Medicine, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian XuDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People’s Republic of ChinaTel/ Fax +86 25 68303453Email xu_jian79@163.comPurpose: Lung cancer is a leading cause of cancer-related death, with lung adenocarcinoma (LUAD) representing the most common subtype. Recently, exosome-based biomarkers have provided new diagnostic approaches for malignancies. We aimed to identify specific exosomal microRNAs (miRNAs) as noninvasive biomarkers for LUAD.Patients and Methods: A total of 110 participants were enrolled and randomly divided into two sets: the discovery set (n=20) and the validation set (n=90). Exosomes were isolated from serum, and miRNAs were subsequently extracted. Candidate miRNAs (miR-21, miR-221-3p, miR-222-3p, miR-223, miR-638 and miR-1290) were detected by quantitative real-time PCR (qRT-PCR) in the discovery set. The upregulated miR-1290 was then selected for further analysis in the validation set along with three tumor markers (CEA, CYFRA21-1 and NSE). The diagnostic and prognostic value of exosomal miR-1290 were estimated through receiver-operating characteristic (ROC) and survival analysis.Results: Serum exosomal miR-1290 was significantly upregulated in LUAD patients compared to healthy controls (P< 0.001) and decreased after resection (P=0.0029). Its expression level was associated with tumor stage, tumor size, lymph node and distant metastasis (all P < 0.05). Exosomal miR-1290 had a higher diagnostic efficacy than CEA, CYFRA21-1 and NSE, with a sensitivity of 80.0% and specificity of 96.7% (AUC: 0.937, 95% CI: 0.890– 0.985; P< 0.001). Moreover, LUAD patients with a high level of exosomal miR-1290 had significantly poorer progression-free survival (PFS) than those with a low level of exosomal miR-1290 (mean PFS: 14 months vs 37 months, P< 0.001). Cox proportional hazards model analysis demonstrated that exosomal miR-1290 could be an independent risk factor for the prognosis of LUAD (HR=7.80, P=0.017).Conclusion: Serum exosomal miR-1290 could be a potential diagnostic and prognostic biomarker for LUAD.Keywords: lung adenocarcinoma, circulating miRNA, exosome, biomarker
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