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1.
Front Immunol ; 15: 1367265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550589

RESUMO

Background: Evidence shows people living with CHB even with a normal ALT (40U/L as threshold) suffer histological disease and there is still little research to evaluate the potential benefit of antiviral benefits in them. Methods: We retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtained their 1-year follow-up data to analyze. Results: ALT levels were categorized into high and low, with thresholds set at >29 for males and >15 for females through Youden's Index. The high normal ALT group showed significant histological disease at baseline (56.43% vs 43.82%, p< 0.001), and better HBV DNA clearance from treatment using PSM (p=0.005). Similar results were obtained using 2016 AASLD high normals (male >30, female >19). Further multivariate logistic analysis showed that high normal ALT (both criterias) was an independent predictor of treatment (OR 1.993, 95% CI 1.115-3.560, p=0.020; OR 2.000, 95% CI 1.055-3.793, p=0.034) Both of the models had higher AUC compared with current scoring system, and there was no obvious difference between the two models (AUC:0.8840 vs 0.8835). Conclusion: Male >30 or female >19 and Male >29 or female>15 are suggested to be better thresholds for normal ALT. Having a high normal ALT in CHB provides a potential benefit in antiviral therapy.


Assuntos
Hepatite B Crônica , Humanos , Masculino , Feminino , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Alanina Transaminase , Estudos Retrospectivos , DNA Viral , Antivirais/uso terapêutico
2.
Clin Chim Acta ; 469: 171-179, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28365450

RESUMO

BACKGROUND: The presence of vascular invasion (VI) in pathology specimens is a well-known unfavorable prognostic factor of hepatocellular carcinoma (HCC) recurrence and overall survival (OS). We investigated the vascular invasion related microRNA (miRNA) expression profiles and potential of prognostic value in HCC. METHODS: MiRNA and mRNA expression data for HCC were accessed from The Cancer Genome Atlas (TCGA). LASSO logistic regression models were used to develop a miRNA-based classifier for predicting VI. The predictive capability was accessed by area under receiver operating characteristics (AUC). Concordance index (C-index) and time-dependent receiver operating characteristic (td-ROC) were used to determine its prognostic value. We validated the predictive and prognostic accuracy of this classifier in an external independent cohort of 127 patients. Functionally relevant targets of miRNAs were determined using miRNA target prediction, experimental validation and correlation of miRNA and mRNA expression data. RESULTS: A 16-miRNA-based classifier was developed which identified VI accurately, with AUC of 0.731 and 0.727 in TCGA set and validation cohort, respectively. C-index and td-ROC showed that the classifier was able to stratify patients into risk groups strongly associated with OS. When stratified by tumor characteristics, the classifier was still a clinically and statistically significant prognostic model. The predictive and prognostic accuracy of the classifier was confirmed in validation cohort. Vascular invasion related miRNA/target pairs were identified by integrating expression patterns of predicted targets, which were validated in cell lines. CONCLUSIONS: A multi-miRNA-based classifier developed based on the presence of VI, which could effectively predict OS in HCC.


Assuntos
Vasos Sanguíneos/patologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , MicroRNAs/genética , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Análise de Sobrevida
3.
Sci Rep ; 6: 25999, 2016 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-27174663

RESUMO

Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Reparo do DNA/genética , Neoplasias Hepáticas/diagnóstico , Família Multigênica/genética , Mutação/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Carcinogênese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Biologia Computacional , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida
5.
Artigo em Inglês | MEDLINE | ID: mdl-26550019

RESUMO

Epidermal growth factor (EGF) and its signaling molecules, EGFreceptor (EGFR) and signal transducer and activator of transcription factor 3 (STAT3), have been considered to play a role in liver fibrosis and cirrhosis. Plumbagin (PL) is an extracted component from the plant and has been used to treat different kinds of cancer. However, its role in regulation of EGFR and STAT3 during liver fibrosis has not been investigated. In this study, the effects of PL on the regulation of EGFR and STAT3 were investigated in carbon tetrachloride (CCl4) induced liver fibrosis and hepatic stellate cells (HSC-T6). PL significantly attenuated liver injury and fibrosis in CCl4 treated rats. At concentrations of 2 to 6 µM, PL did not induce significant cytotoxicity of HSC-T6 cells. Moreover, PL reduced phosphorylation of EGFR and STAT3 in both fibrotic liver and heparin-binding EGF-like growth factor (HB-EGF) treated HSC-T6 cells. Furthermore, PL reduced the expression of α-SMA, EGFR, and STAT3 in both fibrotic liver and HB-EGF treated HSC-T6 cells. In conclusion, plumbagin could ameliorate the development of hepatic fibrosis through its downregulation of EGFR and STAT3 in the liver, especially in hepatic stellate cells.

6.
Oncotarget ; 6(28): 25093-108, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26231037

RESUMO

microRNA (miRNA) expression profiles varied greatly among current studies due to different technological platforms and small sample size. Systematic and integrative analysis of published datesets that compared the miRNA expression profiles between hepatocellular carcinoma (HCC) tissue and paired adjacent noncancerous liver tissue was performed to determine candidate HCC associated miRNAs. Moreover, we further validated the confirmed miRNAs in a clinical setting using qRT-PCR and Tumor Cancer Genome Atlas (TCGA) dataset. A miRNA integrated-signature of 5 upregulated and 8 downregulated miRNAs was identified from 26 published datesets in HCC using robust rank aggregation method. qRT-PCR demonstrated that miR-93-5p, miR-224-5p, miR-221-3p and miR-21-5p was increased, whereas the expression of miR-214-3p, miR-199a-3p, miR-195-5p, miR-150-5p and miR-145-5p was decreased in the HCC tissues, which was also validated on TCGA dataset. A miRNA based score using LASSO regression model provided a high accuracy for identifying HCC tissue (AUC = 0.982): HCC risk score = 0.180E_miR-221 + 0.0262E_miR-21 - 0.007E_miR-223 - 0.185E_miR-130a. E_miR-n = Log 2 (expression of microRNA n). Furthermore, expression of 5 miRNAs (miR-222, miR-221, miR-21 miR-214 and miR-130a) correlated with pathological tumor grade. Cox regression analysis showed that miR-21 was related with 3-year survival (hazard ratio [HR]: 1.509, 95%CI: 1.079-2.112, P = 0.016) and 5-year survival (HR: 1.416, 95%CI: 1.057-1.897, P = 0.020). However, none of the deregulated miRNAs was related with microscopic vascular invasion. This study provides a basis for further clinical application of miRNAs in HCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Biologia Computacional , Perfilação da Expressão Gênica , Neoplasias Hepáticas/genética , MicroRNAs/genética , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Tempo
7.
Immunol Lett ; 162(2 Pt B): 222-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25445618

RESUMO

Previous studies have shown beneficial effects of mesenchymal stem cells (MSCs) transplantation in many autoimmune diseases. However, few studies have focused on the effects of MSCs on autoimmune hepatitis. In our study, we investigated the therapeutic effects of BMSCs (bone mesenchymal stem cells) transplantation in mouse experimental autoimmune hepatitis (EAH) and explored the potential mechanism. BMSCs were injected intravenously into EAH mice. Then, serum levels of ALT and AST, and pathologic alteration of liver tissue were measured to evaluate the liver function and inflammation degree. The expressions of programmed death ligand 1, IL-17 and IL-23 were detected by enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and western blotting. Upon serum biochemical levels and pathological examination, the BMSCs-treated mice especially with multiple dosing administration showed significantly reduction of liver damage. Moreover, the expression of IL-17 was down-regulated by BMSCs intervention as compared to the model group, whereas the PD-L1 and IL-23 were up-regulated following the administration of MSCs. In conclusion, the results of this study suggest that BMSCs transplantation, especially on multiple dosing, may exert immunosuppression effect to ameliorate EAH through the inhibition of IL-17 and up-regulation of PD-L1.


Assuntos
Antígeno B7-H1/imunologia , Hepatite Autoimune/imunologia , Hepatite Autoimune/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Animais , Antígeno B7-H1/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica/imunologia , Hepatite Autoimune/sangue , Hepatite Autoimune/patologia , Interleucina-17/sangue , Interleucina-17/imunologia , Interleucina-23/sangue , Interleucina-23/imunologia , Masculino , Camundongos
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