A novel circulating miRNA-based signature for the early diagnosis and prognosis prediction of non-small-cell lung cancer.

Abstract

BackgroundNon–small‐cell lung cancer (NSCLC) is a significant public health issue worldwide. The aim of our study was to develop a serum miRNA‐based molecular signature for the early detection and prognosis prediction of NSCLC.MethodsThe significantly altered circulating miRNAs were profiled in GSE24709. The top ten upregulated miRNAs were miR‐432, miR‐942, miR‐29c‐5p, miR‐601, miR‐613, miR‐520d‐3p, miR‐1261, miR‐132‐5p, miR‐302b, and miR‐154‐5p, while the top ten downregulated miRNAs were miR‐562, miR‐18b, miR‐9‐3p, miR‐154‐3p, miR‐20b, miR‐18a, miR‐487a, miR‐20a, miR‐103, and miR‐144. Then, the top four upregulated serum miRNAs (miR‐432, miR‐942, miR‐29c‐5p, and miR‐601) were validated by real‐time quantitative PCR. The clinical significance of two candidate serum miRNAs, miR‐942 and miR‐601, was further explored.ResultsOur results showed that the expression levels of serum miR‐942 and serum miR‐601 were significantly upregulated in NSCLC. In addition, serum miR‐942 and serum miR‐601 showed better performance than CEA, CYFRA21‐1, and SCCA for early diagnosis of NSCLC. Combining serum miR‐942 and serum miR‐601 enhanced the efficacy of detecting early‐stage NSCLC. Moreover, high serum miR‐942 and serum miR‐601 were both associated with adverse clinical variables and poor survival. The NSCLC patients with simultaneously high serum miR‐942 and serum miR‐601 suffered worst clinical outcome, while those with simultaneously low serum miR‐942 and serum miR‐601 had most favorable outcome. The multivariate analysis showed that serum miR‐942 and serum miR‐601 were independent prognostic factors for NSCLC.ConclusionsTaken together, serum miR‐942 and serum miR‐601 might serve as a promising molecular signature for the early detection and prognosis prediction of NSCLC.