High expression of miR-16 and miR-451 predicating better prognosis in patients with gastric cancer

Abstract

Purpose: To investigate the expression pattern of miR-16 and miR-451 and evaluate their prognostic value in 180 GC patients undergoing surgery.

Methods: In our previous study, a panel of five circulating miRNAs (miR-16, miR-25, miR-92a, miR-451 and miR-486-5p) can be used as a potential biomarker for detecting of early-stage gastric carcinoma (GC). Tissue microarrays were constructed from 180 patients with GC after surgery. MiR-16 and miR-451 expression was detected by miRNA-locked nucleic acid in situ hybridization, and their relationship with clinicopathological parameters and overall survival was analyzed.

Results: MiR-16 expression was decreased in 30.6 % (55/180) of GC, increased in 54.4 % (98/180) and unchanged in 15.0 % (27/180), compared with paracancerous normal tissue (P < 0.001). MiR-451 expression was decreased in 17.8 % (32/180), increased in 62.8 % (113/180) and unchanged in 19.4 % (35/180) of GC, compared with paracancerous normal tissue (P < 0.001).Univariate analysis indicated that low miR-16 and miR-451 expression, tumor stage, tumor status, node status and tumor size were significant negative prognostic predictors for overall survival in patients with GC (P < 0.001, P < 0.001, P = 0.002, P < 0.001 and P = 0.001, respectively). Multivariate regression analysis demonstrated that stage [hazard ratio (HR) 1.80; 95 % confidence interval (CI) 1.0-3.26; P = 0.05], low expression of miR-16 (HR 2.26; 95 % CI 1.51-3.40; P < 0.001) and miR-451 (HR 2.01; 95 % CI 1.36-2.96; P < 0.001) predicted shorter OS, while tumor status (HR 1.59; 95 % CI 0.73-3.48 P = 0.242), lymph node metastasis (HR 1.41; 95 % CI 0.71-2.82; P = 0.326) and tumor size (HR 1.53; 95 % CI 0.92-2.55; P = 0.099) were not. Moreover, patients with both miR-16 and miR-451 high expression have better OS than those with two miRNAs unchanged or low expression in GC tissues. Patients with both miR-16 and miR-451 high have better OS than patients with single miR-451 high expression.

Conclusions: High expression of miR-16 and miR-451 was associated with longer OS in GC patients. Especially patients with miR-16 and miR-451 double high expression will predict better OS. MiR-16 and miR-451 may be used as novel makers to evaluate prognosis and provide a new treatment target in GC.

Keywords: Gastric cancer (GC); MiR-16; MiR-451; Prognosis.

Fig. 1

MiR-25 levels were stained using in situ hybridization. a MiR-25 staining using in situ hybridization in GC. b MiR-25 staining in adjacent normal tissue; increased miR-25 expression in GC compared with neighboring normal tissue. c MiR-25 staining using in situ hybridization in GC. d MiR-25 staining in adjacent normal tissue; increased miR-25 expression in GC compared with adjacent normal tissue

Fig. 2

Survival curves in patients with GC according to miR-25 levels. a Overall survival curves in 180 patients with GC according to miR-25 levels (P < 0.001). b Survival curves of patients with stage II GC according to miR-25 levels (P = 0.015). c Survival curves of patients with stage III GC according to miR-25 levels (P < 0.001)