C-C motif chemokine ligand 14 (CCL14) is a chemokine promoting the activation of immune cells. However, the relationship between CCL14 expression, tumor immunity, and prognosis in Hepatocellular Carcinoma (HCC) remain unclear. CCL14 expression and its influence on tumor prognosis were analyzed by the ONCOMINE, Tumor Immune Estimation Resource (TIMER) and Kaplan-Meier plotter. The relationship between CCL14 expression and tumor immunity were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). CCL14 expression was significantly lower in several human cancers, including HCC, than in corresponding normal tissues. CCL14 expression in HCC tissues correlated with prognosis. Low CCL14 expression associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in multiple cohorts of HCC patients, particularly at early disease stages (stage 1+2 or grade 2). CCL14 showed strong correlation with tumor-infiltrating B cells, CD4 + and CD8 + T cells, macrophages, neutrophils, and dendritic cells. CCL14 expression in HCC negatively correlated with expression of several immune cell markers, including exhausted T cell markers, PD-1, TIM-3 and CTLA-4, suggesting its role in regulating tumor immunity. These findings demonstrate that CCL14 is a potential prognostic biomarker that determines cancer progression and correlated with tumor immune cells infiltration in HCC.
G2 and S phase-expressed-1 (GTSE1) regulates G1/S cell cycle transition. It was recently reported to be overexpressed in certain human cancers, but its significance and mechanism(s) in hepatocellular carcinoma (HCC) remain unknown. Here, we showed preferential GTSE1 upregulation in human HCC tissues and cell lines that positively correlated with Ki67. GTSE1 knockdown by short hairpin RNA resulted in deficient colony-forming ability and depleted capabilities of HCC cells to migrate and invade. Conversely, exogenous GTSE1 overexpression enhanced colony formation and stimulated HCC cell migration and invasion. Furthermore, GTSE1 silencing was associated with the downregulation of N-cadherin, β-catenin, and Snail, whereas GTSE1 overexpression caused the opposite effects. GTSE1 upregulated Snail via both transcription and protein degradation pathways. Additionally, GTSE1 modulated the sensitivity of HCC to 5-fluorouracil therapy. High GTSE1 correlates with chemo-resistance, while low GTSE1 increases drug sensitivity. Kaplan-Meier survival analysis indicated that high GTSE1 levels were significantly associated with poor overall survival. In conclusion, high expression of GTSE1 is commonly noted in HCC and is closely correlated with migration and invasion by epithelial-to-mesenchymal transition (EMT) modulation. Activated GTSE1 significantly interferes with chemotherapy efficacy and influences the probability of survival of patients with HCC. GTSE1 may thus represent a promising molecular target.
BackgroundTuberculosis (TB) and chronic Hepatitis B virus (HBV) infection are common in China. Fist-line anti-TB medications often produce drug-induced liver injury (DILI). This study sought to investigate whether TB patients with chronic HBV co-infection are more susceptible to liver failure and poor outcomes during anti-TB treatment.MethodsEighty-four TB patients developed DILI during anti-TB treatment and were enrolled, including 58 with chronic HBV co-infection (TB-HBV group) and 26 with TB mono-infection (TB group). Clinical data and demographic characteristics were reviewed. The severity of DILI and incidences of liver failure and death were compared. Risk factors of clinical outcomes were defined.ResultsThe patterns of DILI were similar in both groups. Compared with patients in the TB group, patients in the TB-HBV group who did not receive anti-HBV therapy before anti-TB treatment were more susceptible to Grade-4 severity of DILI (36.2% vs. 7.7%, P = 0.005), liver failure (67.2% vs. 38.5%, P = 0.013) and poor outcomes (37.9% vs. 7.7%, P = 0.005). Age > 50 years (48.1% vs. 22.6%, P = 0.049), cirrhosis (50.0% vs. 15.4%, P = 0.046) and total bilirubin > 20 mg/dl (51.6% vs. 14.8%, P = 0.005) were independent risk factors for the rate of death in the TB-HBV group, and HBV DNA > 20,000 IU/ml had borderline significance (44.1% vs. 20.8%, P = 0.081). In the TB-HBV group, nucleos(t)ide analogues as rescue therapy were not able to reduce short-term death (33.3% vs. 36.8%, P = 0.659) once liver failure had occurred.ConclusionsPatients on anti-TB therapy with chronic HBV co-infection are more susceptible to developing liver failure and having poor outcomes during anti-TB treatment. Regular monitoring of liver function and HBV DNA level is mandatory. Anti-HBV treatment should be considered in those with high viral levels before anti-TB treatment.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3192-8) contains supplementary material, which is available to authorized users.
SummaryElevated programmed death‐1 (PD‐1) has been found in immune cells in viral infections and plays an important role in infection persistence. The soluble form of PD‐1 (sPD‐1) is involved in tumours and viral infections. The aim of this study was to investigate the role of sPD‐1 in chronic hepatitis B (CHB). A total of two hundred and eighteen CHB patients and sixty healthy controls (HC) were enrolled. Demographic data and clinical parameters were collected. An ELISA assay was used to measure serum sPD‐1 levels, and the relationships between sPD‐1 and clinical/virological characteristics was analysed. sPD‐1 levels in CHB patients were higher (median 4.409 IQR 3.435‐5.306 pg/mL) than those of HC individuals (median 0.3665 IQR 0.2425‐0.5010 pg/mL). Among patients at various disease stages, patients with immune activity showed the highest sPD‐1 levels (median 5.138 IQR 4.329‐5.406 pg/mL). sPD‐1 concentration was associated with HBV markers (HBsAg, HBV DNA and HBeAg) and biochemical parameters (serum aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBil] and gamma glutamyl transferase [γ‐GT] levels) (all P < 0.05). sPD‐1 levels were higher in CHB patients with moderate‐to‐severe inflammation or fibrosis than in those with mild inflammation or fibrosis, regardless of ALT levels. The association between sPD‐1 and disease progression of CHB suggests that sPD‐1 could serve as a new indicator in assessing liver fibrosis. These findings may further aid in determining the initiation of antiviral treatment in patients with normal ALT levels.
Background A growing body of evidence suggests that E2Fs, by regulating gene expression related to cell cycle progression and other cellular processes, play a pivotal role in human cancer. However, the distinct roles of each E2F in the development and treatment of hepatocellular carcinoma (HCC) remain unknown. In the present study, the mRNA expression and prognostic value of different E2Fs in HCC are analyzed. Materials and methods Transcriptional and survival data related to E2F expression in patients with HCC were obtained through ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The sequence alteration data for E2Fs were obtained from The Cancer Genome Atlas and c-BioPortal. Gene functional enrichment analyses were performed in Database for Annotation, Visualization and Integrated Discovery. Results The mRNA expression levels of E2F1–E2F8 were all significantly upregulated in HCC patients, and high expression of each E2F was obviously related to poor prognosis. Similarly, the expression of E2Fs showed prognostic prediction value in HCC patients with different cancer stages and pathological grades. Moreover, the mutation rate of E2Fs was relatively high in HCC patients, and the DNA sequence alterations primarily occurred in E2F5, E2F3, and E2F6, which were associated with worse overall survival and disease-free survival in HCC patients. Network analysis confirmed that the expression levels of cell cycle-related genes were mostly affected by E2F mutations. Conclusion High expression of individual E2Fs was associated with poor prognosis in all liver cancer patients. E2Fs may be exploited as good prognostic targets for comprehensive management of HCC patients, but this notion should be further evaluated in clinical studies.
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