BackgroundAccumulating evidences have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers that play key roles in tumor development and progression. Differentiation antagonizing non-protein noding RNA (DANCR) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancers. However, the clinical significance and molecular mechanism of DANCR in bladder cancer is still unknown.MethodsThe relative expression level of DANCR was determined by Real-Time qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell lines. Loss-of-function experiments were performed to investigate the biological roles of DANCR on bladder cancer cell proliferation, migration, invasion and tumorigenicity. Comprehensive transcriptional analysis, RNA-FISH, dual-luciferase reporter assay and western blot were performed to explore the molecular mechanisms underlying the functions of DANCR.ResultsIn this study, we found that DANCR was significantly up-regulated in bladder cancer. Moreover, increased DANCR expression was positively correlated with higher histological grade and advanced TNM stage. Further experiments demonstrated that knockdown of DANCR inhibited malignant phenotypes and epithelial-mesenchymal transition (EMT) of bladder cancer cells. Mechanistically, we found that DANCR was distributed mostly in the cytoplasm and DANCR functioned as a miRNA sponge to positively regulate the expression of musashi RNA binding protein 2 (MSI2) through sponging miR-149 and subsequently promoted malignant phenotypes of bladder cancer cells, thus playing an oncogenic role in bladder cancer pathogenesis.ConclusionThis study is the first to demonstrate that DANCR plays a critical regulatory role in bladder cancer cell and DANCR may serve as a potential diagnostic biomarker and therapeutic target of bladder cancer.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0921-1) contains supplementary material, which is available to authorized users.
BackgroundTo evaluate the prognostic significance of the novel index combining preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) in renal cell carcinoma (RCC) patients.MethodsWe enrolled 1360 patients who underwent nephrectomy in our institution from 2001 to 2010. The cutoff values for HALP, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were defined by using X-tile software. Survival was analyzed by the Kaplan–Meier method, with differences analyzed by the log-rank test. Multivariate Cox proportional-hazards model was used to evaluate the prognostic significance of HALP for RCC.ResultsLow HALP was significantly associated with worse clinicopathologic features. Kaplan-Meier and log-rank tests revealed that HALP was strongly correlated with cancer specific survival (P < 0.001) and Cox multivariate analysis demonstrated that preoperative HALP was independent prognostic factor for cancer specific survival (HR = 1.838, 95%CI:1.260–2.681, P = 0.002). On predicting prognosis by nomogram, the risk model including TNM stage, Fuhrman grade and HALP score was more accurate than only use of TNM staging.ConclusionsHALP was closely associated with clinicopathologic features and was an independent prognostic factor of cancer-specific survival for RCC patients undergoing nephrectomy. A nomogram based on HALP could accurately predict prognosis of RCC.Electronic supplementary materialThe online version of this article (10.1186/s12894-018-0333-8) contains supplementary material, which is available to authorized users.
Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown. Methods: The expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT. Results: SOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype. Conclusion: This study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer.
The outcome of bladder cancer after radical cystectomy is heterogeneous. We aim to evaluate the prognostic value of HALP (hemoglobin, albumin, lymphocyte and platelet) and explore novel prognostic indexes for patients with bladder cancer after radical cystectomy. In this retrospective study, 516 patients with bladder cancer after radical cystectomy were included. The median follow-up was 37 months (2 to 99 mo). Risk factors of decreased overall survival were older age, high TNM stage, high American Society of Anesthesiologists (ASA) grade and low HALP score. The predictive accuracy was better with HALP-based nomogram than TNM stage (C- index 0.76 ± 0.039 vs. 0.708 ± 0.041). By combining ASA grade and HALP, we created a novel index—HALPA score and found it an independent risk factor for decreased survival (HALPA score = 1, HR 1.624, 95% CI 1.139–2.314, P = 0.007; HALPA score = 2, HR 3.471, 95% CI: 1.861–6.472, P < 0.001).The present study identified the prognostic value of HALP and provided a novel index HALPA score for bladder cancer after radical cystectomy.
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