DAX-1 Inhibits Hepatocellular Carcinoma Proliferation by Inhibiting β-Catenin Transcriptional Activity

Background/Aims: The prognostic value of circulating tumor cells (CTC) detected in hepatocellular carcinoma (HCC) patients is currently under debate. We conducted a meta-analysis of available studies to assess its prognostic value for patients diagnosed with HCC. Methods: Medline, Ovid Database, Embase, The Science Citation Index, and Cochrane library, search was conducted on all studies reporting the outcomes of interest. The studies were set up according to the inclusion/exclusion criteria. Using a random-effects model, meta-analysis was performed using hazard ratio (HR), risk ratio (RR) and their 95% confidence intervals (95% CIs) as effect measures. Heterogeneity of the studies was tested for each pooled analysis. Subgroup and sensitivity analyses were also performed. Results: twenty-three published studies that matched the selection criteria were included in this meta-analysis. CTC positivity was significantly associated with Relapse free survival (RFS) (HR 3.03, 95% CI: [1.89-4.86]; p<0.00001) and Overall survival (OS) (HR 2.45, 95% CI: [1.73-3.48]; p<0.00001). CTC positivity were also significantly associated with TNM Stage (RR 1.30, 95% CI: [1.02-1.65]; p=0.03), Tumor size (RR 1.36, 95% CI: [1.09-1.69]; p=0.006), Vascular invasion (RR 1.99, 95% CI: [1.43-2.77]; p<0.0001), Portal vein tumor thrombus (RR 1.73, 95% CI: [1.42-2.11]; p=0.0001), Serum alpha-fetoprotein (AFP) level (RR 2.05, 95% CI: [1.18-3.54]; p=0.01). Conclusion: CTC positivity indicates poor prognosis in patients with hepatocellular carcinoma, and associated with poor clinicopathologic parameters.

Section: Discussionmentioning

confidence: 86%

Circulating Tumor Cells for Predicting the Prognostic of Patients with Hepatocellular Carcinoma: A Meta Analysis

Fan

Yang

Yuan

et al. 2015

“…Transwell chemotaxis assays were carried out to assess HL-60 recruitment to endothelial cells using the 3-μm Millicell inserts (Millipore) [38]. Briefly, HMECs were seeded into 24-well plates and grown until confluent.…”

Section: Hl-60 Chemotaxis and Transmigration Assaymentioning

confidence: 99%

Interleukin-17 Stimulates STAT3-Mediated Endothelial Cell Activation for Neutrophil Recruitment

Yuan

Zhang

Zhuang

et al. 2015

Background/Aims: Interleukin-17 (IL-17) is a major pro-inflammatory cytokine that initiates and maintains inflammation. However, the molecular mechanisms as to how IL-17 influences endothelial cells to promote neutrophil recruitment are not fully understood. Methods: Human endothelial cells (HMECs) were stimulated with IL-17, and investigated for proliferation, migration, and tubule formation activities. Transwell chemotaxis and adhesion assays were performed to assess neutrophil recruitment. Cytokine production was measured by Cytokine Array Chip and ELISA. Western blotting and immunofluorescent analysis were used to detect the phosphorylation and translocation of STAT3. Specific inhibitors, small interfering RNA, and phosphorylation mutants were used to confirm that IL-17 induced STAT3 activation via IL-17RA signaling. Results: Activation of HMECs with IL-17 induced STAT3 phosphorylation and nuclear translocation, which were associated with induction of GRO-α, GM-CSF and IL-8, and neutrophil recruitment. Phosphorylation of STAT3 was identified mainly at the tyrosine in position 705 (Y705), and the Y705F mutants attenuated IL-17-mediated STAT3 activation. Moreover, specific inhibitors, FLLL31, or siRNA silencing of STAT3 attenuated HMECs activation, resulting in inhibition of GRO-α, GM-CSF, IL-8 production, and neutrophil recruitment. Furthermore, phosphorylation of STAT3 was identified as downstream of IL-17RA signaling. Conclusions: IL-17 induced STAT3 activation as a necessary step in endothelial cell activation and neutrophil recruitment.

“…The half of new cases of death occurs in China every year [1][2][3]. The prognosis of patients with HCC is poor and once HCC invades other organs and tissues or spreads distantly, the clinical outcome may be even worse [4][5].…”

Section: Introductionmentioning

confidence: 99%

HULC and Linc00152 Act as Novel Biomarkers in Predicting Diagnosis of Hepatocellular Carcinoma

Wang

Tang

et al. 2015

194

151

Background/Aims: The alterations of long non-coding RNAs (lncRNAs) are related to multiple diseases. They can be detected in plasma as biomarkers for the diagnosis of multiple diseases. In this study, we aimed to determine the expression of circulating lncRNAs in human, which may be promising biomarkers for the diagnosis of hepatocellular carcinoma (HCC). Methods: Eight lncRNAs were chosen as candidates on the basis of the literature to evaluate the diagnostic value and accuracy of the plasma lncRNA profiling system. The candidate lncRNAs were validated by qRT-PCR arranged in the training and validation sets. Additional double-blind testing was performed in 20 patients clinically suspected of having HCC. Results: Circulating HULC and Linc00152 were significantly up-regulated in plasma samples of HCC patients during training set and validation set. Areas under the receiver operating characteristic (ROC) curves of the validated two lncRNAs signature were 0.78 and 0.85, respectively. Combination of HULC and Linc00152 possessed a moderate ability to discrimination between HCC and control with an area under ROC value of 0.87 while the combination of AFP was 0.89 with a positive correlation with tissues expression. Conclusions: Our results suggest that both plasma levels of HULC and Linc00152 achieve a fine diagnostic accuracy in diagnosing ontogenesis and metastasis of HCC and may act as novel biomarkers for HCC.