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

Abstract

Background: Non–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. Methods: The 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. Results: Our 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. Conclusions: Taken together, serum miR-942 and serum miR-601 might serve as a promising molecular signature for the early detection and prognosis prediction of NSCLC.