Ning Wang1,2, Wei Guo2,3, Xingguo Song2,4, Lisheng Liu1,2, Limin Niu1,2, Xianrang Song1,2, Li Xie1,2. 1. Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, P.R. China. 2. Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong Province, P.R. China. 3. Ultrasound Diagnosis Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, P.R. China. 4. Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, P.R. China.
Abstract
Background: Exosomal microRNAs (miRNAs) are proposed to be excellent candidate biomarkers for clinical applications. However, little is known about their potential value as diagnostic biomarkers for metastatic non-small cell lung cancer (NSCLC). Methods: In this study, microarrays were used to determine distinct miRNA profiles of plasma exosomes in a discovery cohort of healthy donors, metastatic NSCLC and nonmetastatic NSCLC patients. Three potential candidate miRNAs were selected based on the differential expression profiles. The discovery set data were validated by quantitative real-time polymerase chain reaction using a validation cohort. Results: NSCLC patients (n = 80) and healthy controls (n = 30) had different exosome-related miRNA profiles in plasma. Results demonstrated that the level of let-7f-5p was decreased in plasma exosomes of NSCLC patients (p < 0.0001). Further analysis of three differentially expressed miRNAs revealed that miR-320a, miR-622 and let-7f-5p levels could significantly segregate patients with metastatic NSCLC from patients with nonmetastatic NSCLC (p < 0.0001, p < 0.0001 and p = 0.023, respectively). In addition, the combination of let-7f-5p, CEA and Cyfra21-1 generated an area under the curve (AUC) of 0.981 for the diagnosis of NSCLC patients, and the combination of miR-320a, miR-622, CEA and Cyfra21-1 had an AUC of 0.900 for the diagnosis of patients with metastatic NSCLC. Conclusions: This novel study demonstrated that plasma exosomal miRNAs are promising noninvasive diagnostic biomarkers for metastatic NSCLC.
Background: Exosomal microRNAs (miRNAs) are proposed to be excellent candidate biomarkers for clinical applications. However, little is known about their potential value as diagnostic biomarkers for metastatic non-small cell lung cancer (NSCLC). Methods: In this study, microarrays were used to determine distinct miRNA profiles of plasma exosomes in a discovery cohort of healthy donors, metastatic NSCLC and nonmetastatic NSCLCpatients. Three potential candidate miRNAs were selected based on the differential expression profiles. The discovery set data were validated by quantitative real-time polymerase chain reaction using a validation cohort. Results:NSCLCpatients (n = 80) and healthy controls (n = 30) had different exosome-related miRNA profiles in plasma. Results demonstrated that the level of let-7f-5p was decreased in plasma exosomes of NSCLCpatients (p < 0.0001). Further analysis of three differentially expressed miRNAs revealed that miR-320a, miR-622 and let-7f-5p levels could significantly segregate patients with metastatic NSCLC from patients with nonmetastatic NSCLC (p < 0.0001, p < 0.0001 and p = 0.023, respectively). In addition, the combination of let-7f-5p, CEA and Cyfra21-1 generated an area under the curve (AUC) of 0.981 for the diagnosis of NSCLCpatients, and the combination of miR-320a, miR-622, CEA and Cyfra21-1 had an AUC of 0.900 for the diagnosis of patients with metastatic NSCLC. Conclusions: This novel study demonstrated that plasma exosomal miRNAs are promising noninvasive diagnostic biomarkers for metastatic NSCLC.