High expression of miR-16 and miR-451 predicating better prognosis in patients with gastric cancer.
OBJECTIVE
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.
Clinical Medical Testing Laboratory, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, No. 98 Western Nantong Road, Yangzhou, 225001, China. renchl@163.com.|Department of Epidemiology and Biostatistics, Ministry of Education (MOE) Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China. renchl@163.com.
Chuanli
C
Ren
Geriatric Medicine, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, China.
Hui
H
Chen
Clinical Medical Testing Laboratory, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, No. 98 Western Nantong Road, Yangzhou, 225001, China.
Chongxu
C
Han
Breast Oncology Surgery, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, China.
Deyuan
D
Fu
Clinical Medical Testing Laboratory, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, No. 98 Western Nantong Road, Yangzhou, 225001, China.
Daxin
D
Wang
College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, China.
Ming
M
Shen
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C505362:MIRN16 microRNA, human; C531201:MIRN451 microRNA, human; D035683:MicroRNAs
Gastric cancer (GC); MiR-16; MiR-451; Prognosis