The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated, which plays an important role in the progression of several cancers. However, the biological role and clinical significance of UCA1 in the carcinogenesis of hepatocellular carcinoma (HCC) remain unclear. Herein, we found that UCA1 was aberrantly upregulated in HCC tissues and associated with TNM stage, metastasis and postoperative survival. UCA1 depletion inhibited the growth and metastasis of HCC cell lines in vitro and in vivo. Furthermore, UCA1 could act as an endogenous sponge by directly binding to miR-216b and downregulation miR-216b expression. In addition, UCA1 could reverse the inhibitory effect of miR-216b on the growth and metastasis of HCC cells, which might be involved in the derepression of fibroblast growth factor receptor 1 (FGFR1) expression, a target gene of miR-216b, and the activation of ERK signaling pathway. Taken together, our data highlights the pivotal role of UCA1 in the tumorigenesis of HCC. Moreover, the present study elucidates a novel lncRNA- miRNA-mRNA regulatory network that is UCA1-miR-216b-FGFR1-ERK signaling pathway in HCC, which may help to lead a better understanding the pathogenesis of HCC and probe the feasibility of lncRNA-directed diagnosis and therapy for this deadly disease.

Accumulating evidences indicate cancer-triggered inflammation plays a pivotal role in carcinogenesis. Systematic inflammatory response biomarkers are considered as potential prognostic factors for improving predictive accuracy in colorectal cancer (CRC). Preoperative neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte- to-monocyte ratio (LMR) were investigated and compared in 205 surgical CRC patients. ROC curve was applied to determine thresholds for four biomarkers, and their prognostic values were assessed using Kaplan-Meier curve, univariate and multivariate COX regression models. Moreover, a number of risk factors were used to form nomograms for evaluating risk of survival, and Harrell's concordance index (c-index) was used to evaluate predictive accuracy. Results showed that elevated NLR was significantly associated with diminished recurrent-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) in surgical CRC patients. Moreover, multivariate COX analysis identified elevated NLR as an independent factor for poor RFS (P < 0.001, HR 2.52, 95% CI 1.65-3.83), OS (P < 0.001, HR 2.73, 95% CI 1.74-4.29) and CSS (P < 0.001, HR 2.77, 95% CI 1.72-4.46). Additionally, predictive nomograms including NLR for RFS, OS and CSS could be more effective in predicting RFS (c-index: 0.810 vs. 0.656), OS (c-index: 0.809 vs. 0.690) and CSS (c-index: 0.802 vs. 0.688) in surgical CRC patients, respectively. These findings indicate that preoperative elevated NLR can be considered as an independent prognostic biomarker for RFS, OS and CSS. Nomograms containing NLR provide improved accuracy for predicting clinical outcomes in surgical CRC patients under surgery resection.

BackgroundInflammation plays an integral role in carcinogenesis and tumor progression. Inflammatory response biomarkers have shown to be promising prognostic factors for improving the predictive accuracy in various cancers. The aim of this study is to investigate the prognostic significance of pre-operative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in gastric cancer (GC).Methods389 patients who had undergone gastrectomy were enrolled from 2007 to 2009 in this study. NLR, dNLR, PLR and LMR were calculated from peripheral blood cell count taken at pre-operation. Receiver operating curve (ROC) was used to determine the optimal cut-off levels for these biomarkers. A predictive model or nomogram was established to predict prognosis for cancer-specific survival (CSS) and disease-free survival (DFS), and the predictive accuracy of the nomogram was determined by concordance index (c-index).ResultsThe median follow-up period was 24 months ranging from 3 months to 60 months. The optimal cut-off levels were 2.36 for NLR, 1.85 for dNLR, 132 for PLR and 4.95 for LMR by ROC curves analysis. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), CSS and DFS, however, elevated LMR showed an adverse effect on worse OS, CSS and DFS. Multivariate analysis revealed that elevated dNLR was an independent factor for worse OS, and NLR was superior to dNLR, PLR and LMR in terms of hazard ratio (HR = 1.53, 95% CI = 1.11-2.11, P = 0.010), which was shown to be independent prognostic indicators for both CSS and DFS. Moreover, the nomogram could more accurately predict CSS (c-index: 0.89) and DFS (c-index: 0.84) in surgical GC patients.ConclusionsPre-operative NLR and dNLR may serve as potential prognostic biomarkers in patients with GC who underwent surgical resection. The proposed nomograms can be used for the prediction of CSS and DFS in patients with GC who have undergone gastrectomy.