Abnormally expressed long non-coding RNAs in prognosis of Osteosarcoma: A systematic review and meta-analysis

Background: Numerous studies have reported the relationship between Long non-coding RNAs (LncRNAs) expression and prognosis of osteosarcoma, but less consensus has been reached. Our meta-analysis was conducted to quantitatively assess the relationship between the expression of LncRNAs, prognosis and clinical pathology in osteosarcoma development. Methods: PubMed, Embase, Web of Science, The Cochrane Library, SionMed, CNKI and WanFang databases were carefully searched to identify eligible studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the prognostic significance of LncRNAs expression in osteosarcoma. Moreover, meta-regression analysis and subgroup analysis were carried out to explore the potential sources of heterogeneity. Results: A total of 20 studies comprising 1749 patients were included in present meta-analysis. The results showed that the over-expression of LncRNA had a significant correlation with overall survival (OS) (HR = 2.16, 95% CI: 1.68-2.79), and was not related to disease free survival (DFS) (HR = 0.71, 95% CI: 0.05-9.53). Subgroup analysis further indicated that LncRNA transcription level was significantly associated with alkaline phosphatase (HR = 2.13, 95% CI: 1.58-2.88), tumor size (< 8/ >= 8: HR = 1.97, 95% CI: 1.55-2.62), metastasis (yes/no: HR = 2.14,95% CI: 1.15-3.97), distant metastasis(presence/absence: HR = 4.02, 95% CI: 3.05-5.23) and Enneking stage(IIA /IIB-III: HR = 3.2, 95% CI: 2.48-4.14), but not associated with age (<= 25/> 25: HR = 1.01, 95% CI: 0.78-1.3), gender(female/male: HR = 1.15, 95% CI: 0.96-1.37), tumor site (femur, tibia/elsewhere: HR = 1.15, 95% CI: 0.94-1.4) and chemotherapy (yes/no: HR = 1.45, 95% CI: 0.46-4.63). Conclusions: This study demonstrated that abnormal LncRNAs expression might be potential prognostic markers to predict worse overall survival in osteosarcoma patients. However, the cut-off values may be the source of heterogeneity.