A comprehensive analysis for associations between multiple microRNAs and prognosis of osteosarcoma patients

Osteosarcoma (OS) is the most common malignant primary bone tumor occurring in children and young adults, which occupies the second important cause of tumor-associated deaths among children and young adults. Recent studies have demonstrated that many microRNAs (miRNAs) have abnormal expression in OS, and can function as prognostic factors of OS patients. However, no previous studies have comprehensively analyzed the relationship between multiple miRNAs and prognosis of OS patients.

A total of 63 OS patients were retrospectively enrolled. The clinical characteristics were collected, and the expression levels of miRNA-21, miRNA-30c, miRNA-34a, miRNA-101, miRNA-133a, miRNA-214, miRNA-218, miRNA-433 and miRNA-539 in tumor tissues were measured through quantitative real-time polymerasechain reaction. Kaplan-Meier analysis was used to perform univariate survival analysis, and Cox regression model was used to perform multivariate survival analysis which included the variables with P < 0.1 in univariate survival analysis.

The cumulative survival for 1, 2 and 5 years was 90.48%, 68.25% and 38.10%, respectively, and mean survival time was (45.39 ± 3.60) months (95% CI [38.34-52.45]). Kaplan-Meier analysis demonstrated that TNM stage, metastasis or recurrence, miRNA-21, miRNA-214, miRNA-34a, miRNA-133a and miRNA-539 were correlated with cum survival, but gender, age, tumor diameter, differentiation, miRNA-30c, miRNA-433, miRNA-101 and miRNA-218 were not. Multivariate survival analysis demonstrated that miRNA-21 (hazard ratio (HR): 3.457, 95% CI [2.165-11.518]), miRNA (HR: 3.138, 95% CI [2.014-10.259]), miRNA-34a (HR: 0.452, 95% CI [0.202-0.915]), miRNA-133a (HR: 0.307, 95% CI [0.113-0.874]) and miRNA-539 (HR: 0.358, 95% CI [0.155-0.896]) were independent prognostic markers of OS patients after adjusting for TNM stage (HR: 2.893, 95% CI [1.496-8.125]), metastasis or recurrence (HR: 3.628, 95% CI [2.217-12.316]) and miRNA-30c (HR: 0.689, 95% CI [0.445-1.828]).

High expression of miRNA-21 and miRNA-214 and low expression of miRNA-34a, miRNA-133a and miRNA-539 were associated with poor prognosis of OS patients after adjusting for TNM stage, metastasis or recurrence and miRNA-30c.