Clinical Values of Long Non-coding RNAs in Bladder Cancer: A Systematic Review

Background: Increasing evidence shows that dysregulated expression of long non-coding RNAs (lncRNAs) can serve as diagnostic or prognostic markers in bladder cancer. The aim of this study was to evaluate the clinical values of dysregulated lncRNAs in bladder cancer. Methods: Eligible studies were systematically searched in PubMed, Embase, and Web of Science databases from inception to December 2017. Odds ratios (OR) were calculated to investigate the correlation between lncRNAs and clinicopathological parameters. Pooled hazard ratios (HR) and 95% confidence interval (CI) were calculated to explore the prognostic value of lncRNAs in bladder cancer. Pooled diagnostic parameters were also calculated to estimate the performance of lncRNAs in diagnosing bladder cancer. All statistical analyses were performed by using STATA 13.1 program. Results: A total of 37 relevant studies were included to the present systematic review according to the inclusion and exclusion criteria, including 26 on clinicopathological parameters, 19 on prognosis, and 7 on diagnosis. For clinicopathological parameters, MALAT1 expression was significantly associated with lymph node metastasis (OR = 2.731; 95% CI: 1.409-5.292; p = 0.003), and high-level expression of XIST was related to larger tumor size (OR = 2.473; 95% CI: 1.159-5.276; p = 0.019) and higher TNM stage (OR = 0.400; 95% CI, 0.184-0.868; p = 0.020). For the prognostic values, the most significant association was observed between increased expressions of SPRY4-IT1 and poor overall survival (OS) (HR = 3.716; 95% CI: 2.084-6.719; p < 0.001); high MALAT1 expression was significantly associated with poor OS (HR = 1.611; 95% CI: 1.076-2.412; p = 0.020). For the diagnostic values, UCA1 expression profile achieved a combined AUC of 0.92, with sensitivity of 0.84 and specificity of 0.89 in distinguishing patients with bladder cancer from non-cancerous controls. Conclusions: In summary, systematic review elaborated that abnormal lncRNAs expression can serve as potential markers for prognostic evaluation in bladder cancer patients. In addition, the diagnostic meta-analysis concluded that abnormally expressed UCA1 can function as potential diagnostic markers for bladder cancer.