Low miR-34a and miR-192 are associated with unfavorable prognosis in patients suffering from osteosarcoma.

Abstract

P53 is a well-known tumor suppressor gene involved in malignancy. Many microRNAs (miRNAs) have recently been identified as key components of p53 signaling networks, owing to the central role of p53 in many processes, these p53-regulated miRNAs may possess important role in osteosarcoma. The expression of six p53-related miRNAs (miR-34 family [including miR-34a, 34b and 34c], miR-31, miR-192, and miR-215) in 80 pairs of osteosarcoma and corresponding noncancerous bone tissues were estimated by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the associations of miRNAs expression with clinicopathological factors, p53 status, and survival of patients were analyzed. We found that among all six miRNAs, miR-34 family, -192, and -215 had decreased levels, whereas the level of miR-31 was increased (p<0.05) in tumor compared with corresponding noncancerous bone tissues, and miR-192/215 in patients with p53 positive expression was lower than those with negative p53. Kaplan-Meier analysis demonstrated that osteosarcoma patients with low miR-34a (P=0.000) and miR-192 (P=0.022) expression had poorer disease-free survival (DFS). Moreover, disease-free survival (DFS) was shorter for patients with low miR-34a and miR-192 expression (P=0.007) and the combination of low miR-192 with p53 positive expression (P=0.000). Furthermore, the multivariate analysis identified that low miR-34a expression, the combination of low miR-34a and miR-192 expression levels and the combination of low miR-192 with p53 positive were independent biomarkers of shorter DFS. Together, these results suggest that p53-associated miR-34a and miR-192 expression could be novel prognosis biomarkers for surgically treated osteosarcoma.