Li Wei, He Xijing, Xue Rongliang, Zhang Ying, Zhang Xiaoqin, Lu Jianrui, Zhang Zhenni, Xue Li
Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China; Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Pathol Res Pract. 2016 Oct;212(10):861-866. doi: 10.1016/j.prp.2016.06.013. Epub 2016 Jun 27.
LncRNA hypoxia-inducible factor-2α (HIF-2α) promoter upstream transcript (HIF2PUT) functions as a novel regulatory factor of osteosarcoma stem cells partly by controlling HIF-2α expression. The aim of this study was to investigate the clinical significance of HIF-2α and HIF2PUT in human osteosarcoma.
Quantitative real-time PCR was performed to detect the expression levels of HIF-2α mRNA and HIF2PUT in 82 surgical specimens of primary osteosarcoma and matched non-cancerous bone tissues. Then, the associations of HIF-2α and/or HIF2PUT expression with various clinicopathological features of osteosarcoma patients were statistically analyzed. Moreover, their prognostic value was further evaluated.
Compared with non-cancerous bone tissues, HIF-2α mRNA and HIF2PUT expression were both significantly upregulated in osteosarcoma tissues (all P<0.001). Interestingly, the expression levels of HIF-2α mRNA in osteosarcoma tissues were positively correlated with those of HIF2PUT (r=0.28, P=0.009). Additionally, osteosarcoma patients with HIF-2α mRNA and/or HIF2PUT over-expression more frequently had large tumor size (all P<0.05), advanced clinical stage (all P<0.01) and positive distant metastasis (all P<0.01). Moreover, osteosarcoma patients with HIF-2α mRNA and/or HIF2PUT over-expression had a significantly shorter overall and disease-free survival (all P<0.05). Furthermore, Cox multivariate analysis identified that HIF-2α mRNA and/or HIF2PUT expression, clinical stage and distant metastasis were all independent and significant prognostic factors for both overall and disease-free survival (all P<0.05).
HIF-2α and HIF2PUT upregulation may be a common feature in human osteosarcomas with aggressive potency. The over-expression of the two molecules, alone or combined, may predict poor prognosis in osteosarcoma patients.
长链非编码RNA缺氧诱导因子-2α（HIF-2α）启动子上游转录本（HIF2PUT）部分通过控制HIF-2α表达，作为骨肉瘤干细胞的一种新型调控因子发挥作用。本研究旨在探讨HIF-2α和HIF2PUT在人类骨肉瘤中的临床意义。
采用定量实时PCR检测82例原发性骨肉瘤手术标本及配对的非癌性骨组织中HIF-2α mRNA和HIF2PUT的表达水平。然后，对HIF-2α和/或HIF2PUT表达与骨肉瘤患者各种临床病理特征的相关性进行统计学分析。此外，进一步评估它们的预后价值。
与非癌性骨组织相比，骨肉瘤组织中HIF-2α mRNA和HIF2PUT表达均显著上调（均P<0.001）。有趣的是，骨肉瘤组织中HIF-2α mRNA表达水平与HIF2PUT表达水平呈正相关（r=0.28，P=0.009）。此外，HIF-2α mRNA和/或HIF2PUT过表达的骨肉瘤患者更常出现肿瘤体积大（均P<0.05）、临床分期晚（均P<0.01）和远处转移阳性（均P<0.01）。此外，HIF-2α mRNA和/或HIF2PUT过表达的骨肉瘤患者总生存期和无病生存期显著缩短（均P<0.05）。此外，Cox多因素分析确定HIF-2α mRNA和/或HIF2PUT表达、临床分期和远处转移均是总生存期和无病生存期的独立且显著的预后因素（均P<0.05）。
HIF-2α和HIF2PUT上调可能是具有侵袭性的人类骨肉瘤的一个共同特征。这两种分子单独或联合过表达可能预示骨肉瘤患者预后不良。
