MicroRNA-145 downregulation associates with advanced tumor progression and poor prognosis in patients suffering osteosarcoma

Mingjie Tang,^1,# Lijun Lin,^2,# Haikang Cai,³ Jie Tang,³ Zubin Zhou<sup>1

1</sup>Department of Orthopedics, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, ²Department of Orthopedics, Zhujiang Hospital, The Southern Medical University, Guangzhou, ³Department of Orthopedics, Xuhui Central Hospital, Shanghai, People’s Republic of China

#These authors contributed equally to this work

Purpose: Microribonucleic acid (miRNA)-145 (miR-145) has been identified as a tumor suppressor in several types of human cancers. Especially, miR-145 expression has been found to be significantly decreased in osteosarcoma tissues, and enforced expression of this miRNA could inhibit invasion and angiopoiesis of osteosarcoma cells. However, its clinical significance in osteosarcoma is still unclear. Therefore, the aim of this study was to analyze the association of miR-145 expression with clinicopathologic features and prognosis in patients suffering osteosarcoma.
Methods: miR-145 expression was detected by quantitative real-time reverse transcriptase polymerase chain reaction analysis using 166 pairs of osteosarcoma and noncancerous bone tissues. Then, the associations of miR-145 expression with clinicopathological factors or survival of patients suffering osteosarcoma were determined.
Results: The expression levels of miR-145 in osteosarcoma tissues were significantly lower than those in corresponding noncancerous bone tissues (P < 0.0001). In addition, miR-145 downregulation more frequently occurred in osteosarcoma specimens with advanced clinical stage (P = 0.003) and positive distant metastasis (P = 0.008). Moreover, the univariate analysis demonstrated that osteosarcoma patients with low miR-145 expression had poorer overall (P = 0.003) and disease-free survival (P < 0.001). Furthermore, the multivariate analysis identified low miR-145 expression as an independent prognostic factor for both overall (P = 0.01) and disease-free survival (P = 0.008).
Conclusion: For the first time, the current data offer convincing evidence that the downregulation of miR-145 may be associated with tumor aggressiveness and tumor metastasis of osteosarcoma, and that this miRNA may be an independent prognostic marker for osteosarcoma patients.

Keywords: osteosarcoma, miR-145, prognosis, overall survival, disease-free survival