Department of Orthopedics, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Onco Targets Ther. 2013 Jul 8;6:833-8. doi: 10.2147/OTT.S40080. Print 2013.
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.
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.
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).
For the first time, the current data offer convincing evidence that the down-regulation 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.
微小 RNA-145(miR-145)已被鉴定为几种人类癌症中的肿瘤抑制因子。特别是,miR-145 的表达在骨肉瘤组织中显著降低,并且强制表达这种 miRNA 可以抑制骨肉瘤细胞的侵袭和血管生成。然而,其在骨肉瘤中的临床意义仍不清楚。因此,本研究旨在分析 miR-145 表达与骨肉瘤患者临床病理特征和预后的关系。
通过定量实时逆转录聚合酶链反应分析检测 166 对骨肉瘤和非癌性骨组织中的 miR-145 表达。然后,确定 miR-145 表达与骨肉瘤患者临床病理因素或生存的关系。
骨肉瘤组织中的 miR-145 表达水平明显低于相应的非癌性骨组织(P<0.0001)。此外,miR-145 下调更频繁地发生在具有晚期临床分期(P=0.003)和阳性远处转移(P=0.008)的骨肉瘤标本中。此外,单因素分析表明,miR-145 低表达的骨肉瘤患者总体生存率(P=0.003)和无病生存率(P<0.001)较差。此外,多因素分析确定 miR-145 低表达是总体生存率(P=0.01)和无病生存率(P=0.008)的独立预后因素。
首次提供令人信服的证据表明,miR-145 的下调可能与骨肉瘤的肿瘤侵袭性和肿瘤转移有关,并且该 miRNA 可能是骨肉瘤患者的独立预后标志物。