Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma

• Published in: Tumor biology Vol. 37; no. 4; pp. 4445 - 4455
• Main Authors: Ma, Bing, Li, Meng, Zhang, Lei, Huang, Ming, Lei, Jun-Bin, Fu, Gui-Hong, Liu, Chun-Xin, Lai, Qi-Wen, Chen, Qing-Quan, Wang, Yi-Lian
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.04.2016; Springer Nature B.V
• Subjects: Adolescent; Adult; Alkaline Phosphatase - metabolism; Area Under Curve; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Bone cancer; Bone Neoplasms - blood; Bone Neoplasms - diagnosis; Bone Neoplasms - genetics; Bone Neoplasms - mortality; Cancer Research; Case-Control Studies; Disease-Free Survival; Epigenetics; Female; Gene Expression; Humans; Kaplan-Meier Estimate; Male; Medical prognosis; Middle Aged; Multivariate Analysis; Original Article; Osteosarcoma - blood; Osteosarcoma - diagnosis; Osteosarcoma - genetics; Osteosarcoma - mortality; Pathogenesis; Polymerase chain reaction; Prognosis; Proportional Hazards Models; Ribonucleic acid; RNA; RNA, Long Noncoding - blood; RNA, Long Noncoding - genetics; ROC Curve; Up-Regulation; Young Adult; lncRNA; Prognosis; TUG1; Osteosarcoma
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-015-4301-6

The pathogenesis of osteosarcoma involves complex genetic and epigenetic factors. This study was to explore the impact and clinical relevance of long non-coding RNA (lncRNA), Taurine up-regulated gene 1 (TUG1) on patients with osteosarcoma. Seventy-six osteosarcoma tissues and matched adjacent normal tissues were included for analysis. The plasma samples were obtained from 29 patients with osteosarcoma at pre-operation and post-operation, 42 at newly diagnosed, 18 who experienced disease progression or relapse, 45 post-treatment, 36 patients with benign bone tumor, and 20 healthy donors. Quantitative real-time reverse transcript polymerase chain reactions were used to assess the correlation of the expression levels of TUG1 with clinical parameters of osteosarcoma patients. TUG1 was significantly overexpressed in the osteosarcoma tissues compared with matched adjacent normal tissues ( P  < 0.01) and was closely correlated with tumor size, post-operative chemotherapy, and Enneking surgical stage. Upregulation of TUG1 strongly correlated with poor prognosis and was an independent prognostic indicator for overall survival (HR = 2.78, 95% CI = 1.29–6.00, P  = 0.009) and progression-free survival (HR = 1.81, 95% CI = 1.01–3.54, P  = 0.037). Our constructed nomogram containing TUG1 had more predictive accuracy than that without TUG1 (c-index 0.807 versus 0.776, respectively). In addition, for plasma samples, TUG1 expression levels were obviously decreased in post-operative patients (mean ΔC T −4.98 ± 0.22) compared with pre-operation patients (mean ΔC T −6.09 ± 0.74), and the changes of TUG1 expression levels were significantly associated with disease status. Receiver operating characteristic (ROC) curve analysis demonstrated that TUG1 could distinguish patients with osteosarcoma from healthy individuals compared with alkaline phosphatase (ALP) (the area under curve 0.849 versus 0.544). TUG1 was overexpressed in patients with osteosarcoma and strongly correlated with disease status. In addition, TUG1 may serve as a molecular indicator in maintaining surveillance and forecasting prognosis.