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.

Keywords: early diagnosis; non–small‐cell lung cancer; prognosis prediction; serum miR‐601; serum miR‐942.

FIGURE 1

Validating the top four upregulated serum miRNAs in GSE24709. A, The expression level of serum miR‐942 was significantly increased in NSCLC patients compared to the healthy controls. B, Serum miR‐601 was markedly upregulated in NSCLC cases. C, The level of serum miR‐29c‐5p was slightly increased in patients with NSCLC. D, No significant difference was found for serum miR‐432 between NSCLC patients and healthy controls

FIGURE 2

Serum miR‐942 and serum miR‐601 were significantly increased in NSCLC. A, The expression level of serum miR‐942 was dramatically upregulated in patients with NSCLC compared to patients with benign lung diseases and healthy controls. B, The serum miR‐601 level was higher in patients with NSCLC than in patients with benign lung diseases and healthy controls

FIGURE 3

The diagnostic value of serum miR‐942 and serum miR‐601 for early‐stage NSCLC. A, The diagnostic performance of serum miR‐942 for discriminating early‐stage NSCLC from healthy controls. B, The diagnostic performance of serum miR‐601 for discriminating early‐stage NSCLC from healthy controls. C, The diagnostic performance of combining serum miR‐942 and serum miR‐601 for discriminating early‐stage NSCLC from healthy controls. D‐F, The diagnostic performance of CEA, CYFRA21‐1, and SCCA for discriminating early‐stage NSCLC from healthy controls

FIGURE 4

The association between serum miR‐942/serum miR‐601 and OS/RFS in NSCLC. A‐B, The NSLCC patients in the high serum miR‐942 group had poorer OS and RFS than the patients in the low serum miR‐942 group. C‐D, The NSLCC patients in the high serum miR‐601 group had shorter OS and RFS than the patients in the low serum miR‐601 group

FIGURE 5

The prognostic value of combining serum miR‐942 and serum miR‐601 in NSCLC. (A‐B) Worst OS and RFS were observed in the patients from high serum miR‐942+ high serum miR‐601 group, while the patients in the low serum miR‐942+ low serum miR‐601 group had the most favorable OS and RFS