Identification of Circulating miR-762 as a Novel Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer

Abstract

Background: MicroRNAs (miRNAs) have been demonstrated to play critical roles in tumorigenesis of non-small cell lung cancer (NSCLC), and circulating miRNAs are a valuable source of biomarkers for the clinical management of NSCLC. The aim of this study was to determine the value of serum miR-762 as a diagnostic and prognostic biomarker for NSCLC. Methods: We examined circulating miR-762 expression in 148 NSCLC patients and 60 healthy individuals using the quantitative real-time polymerase chain reaction (qRT-PCR). The effect of miR-762 downregulation on the proliferative capacity of NSCLC cells were also explored. Results: The serum miR-762 levels were significantly upregulated in NSCLC patients compared to the healthy individuals. Receiver operating characteristics (ROC) curve analysis revealed that circulating miR-762, carcinoembryonic antigen (CEA), CYFRA21-1 and a combination of these 3 biomarkers yield the areas under the curve (AUC) of 0.874, 0.826, 0.41 and 0.969, respectively. Interestingly, circulating miR-762 identified the NSCLC patients at the clinical stage I from healthy controls with an AUC value of 0.920. In addition, serum miR-762 expression was significantly correlated with clinical stage, lymph node metastasis, histological grade and gefitinib-resistance. The survival analysis showed that NSCLC patients in the high serum miR-762 group suffered worse overall survival and relapse-free survival than those in the low serum miR-762 group. The multivariate Cox proportional hazards regression analysis revealed high circulating miR-762 was an independent unfavorable prognostic factor. Downregulation of miR-762 significantly suppressed the proliferative capacity of NSCLC cells in vitro , and bioinformatic analysis of the potential downstream targets of miR-762 identified many important cancer-associated pathways. Conclusions: In conclusion, serum miR-762 might serve as a promising diagnostic and prognostic biomarker for the NSCLC.