scholarly journals Diagnostic and Prognostic Value of miR-16, miR-146a, miR-192 and miR-221 in Exosomes of Hepatocellular Carcinoma and Liver Cirrhosis Patients

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2484
Author(s):  
Thorben Fründt ◽  
Linda Krause ◽  
Elaine Hussey ◽  
Bettina Steinbach ◽  
Daniel Köhler ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Regression Model ◽  
Prognostic Value ◽  
Cox Regression ◽  
Healthy Individuals ◽  
Poor Overall Survival ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas ◽  
Diagnostic And Prognostic Value

We aimed to identify a specific microRNA (miRNA) pattern to determine diagnostic and prognostic value in plasma exosomes of hepatocellular carcinoma (HCC) patients. A two-stage study was carried out: exosomal miRNAs were quantified in plasma of HCC patients and healthy individuals by PCR-based microarray cards containing 45 different miRNAs (training cohort). Then, four deregulated miRNAs (miR-16, miR-146a, miR-192, and miR-221) were quantified in the validation analysis using exosomes derived from 85 HCC patients, 50 liver cirrhosis patients, and 20 healthy individuals. Exosomal miR-146a (p = 0.0001), miR-192 (p = 0.002) and miR-221 (p = 0.032) were upregulated only in HCC patients. Repeated 10-fold cross validation showed that miR-146a differentiated HCC from liver cirrhosis patients with AUC of 0.80 ± 0.14 (sensitivity: 81 ± 13%, specificity: 58 ± 22%) in a logistic regression model. High miR-192 presence is associated with poor overall survival (OS) in all HCC patients (p = 0.027) and was predictor of OS in HCC patients in an uni- and multivariate Cox regression model. Moreover, decreased miR-16 levels correlated with OS in liver cirrhosis patients (p = 0.034). Our results emphasized that exosomes secreted into the plasma carry differentially expressed miRNAs of which in particular, miR-192, miR-146, and miR-16 are promising diagnostic and prognostic markers for both HCC and liver cirrhosis patients.

scholarly journals The diagnostic and prognostic value of H2AFY in hepatocellular carcinoma

2020 ◽  
Author(s):  
xuyang ma ◽  
Ying Ding ◽  
Li Zeng
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Normal Liver ◽  
Diagnostic Value ◽  
The Relationship ◽  
Diagnostic And Prognostic Value

Abstract Background: The potential correlation between H2AFY (also known as MacroH2A1) and the clinical characteristics of hepatocellular carcinoma (HCC) patients was analysed through gene expression profiles and clinical data in The Cancer Genome Atlas (TCGA) database, and the diagnostic and prognostic value of H2AFY in HCC was discussed. Methods: The gene expression data of HCC and the corresponding clinical characteristics of HCC patients were downloaded from the TCGA database. The differences in H2AFY in normal liver tissues and HCC were analysed. The relationship between H2AFY and clinical characteristics was analysed by Wilcoxon signed-rank test, logistic regression and Kruskal-Wallis test. The Kaplan-Meier method and the Cox regression method were used to analyse the relationship between overall survival and clinical characteristics of the patients. An ROC curve was used to predict the diagnostic value of H2AFY in HCC. Gene set enrichment analysis (GSEA) was used to analyse the pathway enrichment of H2AFY. Result: Compared with normal liver tissues, H2AFY was significantly highly expressed in HCC. H2AFY was positively correlated with the age, clinical stage, G stage (grade) and T stage (tumor stage) of liver cancer patients. Higher H2AFY expression predicted a poor prognosis in HCC patients. Cox regression analysis suggested that H2AFY was an independent risk factor for the prognosis of HCC patients. The ROC curve suggested that H2AFY had certain diagnostic value in HCC. GSEA suggested that H2AFY was correlated with lipid metabolism and a variety of tumour pathways. Conclusion: Our study showed that H2AFY was significantly overexpressed in HCC. H2AFY may be a potential diagnostic and prognostic marker for HCC, and high expression of H2AFY predicts a poor prognosis in patients with HCC.

scholarly journals The diagnostic and prognostic value of H2AFY in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuyang Ma ◽  
Ying Ding ◽  
Li Zeng
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Normal Liver ◽  
Diagnostic Value ◽  
The Relationship ◽  
Diagnostic And Prognostic Value

Abstract Background The potential correlation between H2AFY (also known as MacroH2A1) and the clinical characteristics of hepatocellular carcinoma (HCC) patients was analysed through gene expression profiles and clinical data in The Cancer Genome Atlas (TCGA) database, and the diagnostic and prognostic value of H2AFY in HCC was discussed. Methods The gene expression data of HCC and the corresponding clinical characteristics of HCC patients were downloaded from the TCGA database. The differences in H2AFY in normal liver tissues and HCC were analysed. The relationship between H2AFY and clinical characteristics was analysed by Wilcoxon signed-rank test, logistic regression and Kruskal-Wallis test. The Kaplan-Meier method and the Cox regression method were used to analyse the relationship between overall survival and clinical characteristics of the patients. An ROC curve was used to predict the diagnostic value of H2AFY in HCC. Gene set enrichment analysis (GSEA) was used to analyse the pathway enrichment of H2AFY. Result Compared with normal liver tissues, H2AFY was significantly highly expressed in HCC. H2AFY was positively correlated with the age, clinical stage, G stage (grade) and T stage (tumor stage) of liver cancer patients. Higher H2AFY expression predicted a poor prognosis in HCC patients. Cox regression analysis suggested that H2AFY was an independent risk factor for the prognosis of HCC patients. The ROC curve suggested that H2AFY had certain diagnostic value in HCC. GSEA suggested that H2AFY was correlated with lipid metabolism and a variety of tumour pathways. Conclusion Our study showed that H2AFY was significantly overexpressed in HCC. H2AFY may be a potential diagnostic and prognostic marker for HCC, and high expression of H2AFY predicts a poor prognosis in patients with HCC.

scholarly journals The diagnostic and prognostic value of H2AFY in hepatocellular carcinoma

2020 ◽  
Author(s):  
xuyang ma ◽  
Ying Ding ◽  
Li Zeng
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Normal Liver ◽  
Diagnostic Value ◽  
The Relationship ◽  
Diagnostic And Prognostic Value

Abstract Background The potential correlation between H2AFY (also known as MacroH2A1) and the clinical characteristics of hepatocellular carcinoma (HCC) patients was analysed through gene expression profiles and clinical data in The Cancer Genome Atlas (TCGA) database, and the diagnostic and prognostic value of H2AFY in HCC was discussed. Methods The gene expression data of HCC and the corresponding clinical characteristics of HCC patients were downloaded from the TCGA database. The differences in H2AFY in normal liver tissues and HCC were analysed. The relationship between H2AFY and clinical characteristics was analysed by Wilcoxon signed-rank test, logistic regression and Kruskal-Wallis test. The Kaplan-Meier method and the Cox regression method were used to analyse the relationship between overall survival and clinical characteristics of the patients. An ROC curve was used to predict the diagnostic value of H2AFY in HCC. Gene set enrichment analysis (GSEA) was used to analyse the pathway enrichment of H2AFY. Result Compared with normal liver tissues, H2AFY was significantly highly expressed in HCC. H2AFY was positively correlated with the age, clinical stage, G stage and T stage of liver cancer patients. Higher H2AFY expression predicted a poor prognosis in HCC patients. Cox regression analysis suggested that H2AFY was an independent risk factor for the prognosis of HCC patients. The ROC curve suggested that H2AFY had certain diagnostic value in HCC. GSEA suggested that H2AFY was correlated with lipid metabolism and a variety of tumour pathways. Conclusion Our study showed that H2AFY was significantly overexpressed in HCC. H2AFY may be a potential diagnostic and prognostic marker for HCC, and high expression of H2AFY predicts a poor prognosis in patients with HCC.

scholarly journals Can Serum Glypican-3 Be a Biomarker for Effective Diagnosis of Hepatocellular Carcinoma? A Meta-Analysis of the Literature

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Sheng-Li Yang ◽  
Xiefan Fang ◽  
Zao-Zao Huang ◽  
Xiang-Jie Liu ◽  
Zhi-Fan Xiong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Sensitivity And Specificity ◽  
Meta Analysis ◽  
Diagnostic Value ◽  
Healthy Individuals ◽  
Subgroup Analyses ◽  
Effective Diagnosis ◽  
Diagnostic Index

Objective. This review is to evaluate the diagnostic value of serum GPC3 for hepatocellular carcinoma (HCC) due to conflicting results reported.Methods. NCBI PubMed and Embase were comprehensively searched for studies that have used serum GPC3 level as a diagnostic index for HCC. The quality of the included studies was assessed. Subgroup analyses were conducted to evaluate the sensitivity and specificity of GPC3 as a HCC marker. Statistical analysis was performed with the software STATA version 12.0.Results. A total of 22 studies were included. The qualities of included studies were relatively poor. Among them, 18 studies have shown that serum GPC3 is a specific biomarker for HCC, and the pooled sensitivity and specificity of these studies were 69 and 93%, respectively. The other 4 studies have reported conflicting results, which were not caused by races, infection status of HBV and HCV, or assay reagents but due to one common experimental design of enrolling liver cirrhosis patients as control subjects.Conclusions. This meta-analysis indicates that serum GPC3 is elevated in HCC patients compared with healthy individuals, but more studies are needed to evaluate its effectiveness to differentially diagnose HCC and liver cirrhosis.

scholarly journals Constructing the Logical Regression Model to Predict the Target of Jianpi Jiedu Decoction in the Treatment of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rongjie Zhang ◽  
Yan Chen ◽  
Ge Zhou ◽  
Baoguo Sun ◽  
Yue Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Regression Model ◽  
Target Genes ◽  
Cox Regression ◽  
Risk Group ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Prognostic Analysis ◽  
Significant Difference

Objectives. The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods. The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results. 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group ( p < 0.05 ). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues ( p < 0.05 ). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC ( p < 0.05 ). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions. In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1.

scholarly journals Identification of Hypoxia-Related Differentially Expressed Genes and Construction of the Clinical Prognostic Predictor in Hepatocellular Carcinoma by Bioinformatic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Hao Guo ◽  
Jing Zhou ◽  
Yanjun Zhang ◽  
Zhi Wang ◽  
Likun Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Model ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Clinical Prognosis ◽  
Prognostic Predictor ◽  
Key Genes

Background. Hypoxia closely relates to malignant progression and appears to be prognostic for outcome in hepatocellular carcinoma (HCC). Our research is aimed at mining the hypoxic-related genes (HRGs) and constructing a prognostic predictor (PP) model on clinical prognosis in HCC patients. Methods. RNA-sequencing data about HRGs and clinical data of patients with HCC were obtained from The Cancer Genome Atlas (TCGA) database portal. Differentially expressed HRGs between HCC and para-carcinoma tissue samples were obtained by applying the Wilcox analysis in R statistical software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene functional enrichment analyses. Then, the patients who were asked to follow up for at least one month were enrolled in the following study. Cox proportional risk regression model was applied to obtain key HRGs which related to overall survival (OS) in HCC. PP was constructed and defined, and the accuracy of PP was validated by constructing the signature in a training set and validation set. Connectivity map (CMap) was used to find potential drugs, and gene set cancer analysis (GSCA) was also performed to explore the underlying molecular mechanisms. Results. Thirty-seven differentially expressed HRGs were obtained. It contained 28 upregulated and 9 downregulated genes. After the univariate Cox regression model analysis, we obtained 27 prognosis-related HRGs. Of these, 25 genes were risk factors for cancer, and 2 genes were protective factors. The PP was composed by 12 key genes (HDLBP, SAP30, PFKP, DPYSL4, SLC2A1, HMOX1, PGK1, ERO1A, LDHA, ENO2, SLC6A6, and TPI1). GSCA results showed the overall activity of these 12 key genes in 10 cancer-related pathways. Besides, CMap identified deferoxamine, crotamiton, talampicillin, and lycorine might have effects with HCC. Conclusions. This study firstly reported 12 prognostic HRGs and constructed the model of the PP. This comprehensive research of multiple databases helps us gain insight into the biological properties of HCC and provides deferoxamine, crotamiton, talampicillin, and lycorine as potential drugs to fight against HCC.

Role of BCYRN1 in hepatocellular carcinoma pathogenesis by lncRNA–miRNA–mRNA network analysis and its diagnostic and prognostic value

Epigenomics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1209-1231 ◽  
Author(s):  
Xin-Liang Ming ◽  
Yan-Lin Feng ◽  
Ding-Dong He ◽  
Chang-Liang Luo ◽  
Jia-Ling Rong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Data Mining ◽  
Microarray Data ◽  
Prognostic Value ◽  
Prognostic Biomarker ◽  
Tumor Node Metastasis ◽  
Comprehensive Strategy ◽  
Node Metastasis ◽  
Diagnostic And Prognostic Value

Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results: BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA–miRNA–mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.

scholarly journals Treg/Th17 imbalance and its clinical significance in patients with hepatitis B-associated liver cirrhosis

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Yong-Ting Lan ◽  
Zhen-li Wang ◽  
Peng Tian ◽  
Xiao-Na Gong ◽  
Yu-Chen Fan ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Regression Model ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Decompensated Liver Cirrhosis ◽  
Cox Regression Model ◽  
Potential Marker

Abstract Background Recent studies have shown that T cell-mediated cellular immune mechanisms play important roles in the progression of hepatitis B to liver cirrhosis, but the underlying mechanisms remain unclear. This present study was aimed to determine the relationship between Treg/Th17 and hepatitis B-associated liver cirrhosis. Methods The Treg and Th17 cell frequencies in the peripheral blood of all participants, including 93 patients with hepatitis B-associated liver cirrhosis and 40 healthy subjects, were measured by flow cytometer. Cox regression model and receiver operating characteristic(ROC) curves were applied to investigate the prognostic significance of Treg/Th17 ratio in decompensated liver cirrhosis. Results We observed the Treg/Th17 imbalance was present in patients with hepatitis B-associated liver cirrhosis, with reduced Treg cells in their peripheral blood, increased Th17 cells and decreased Treg/Th17 ratio. Treg and Th17 cells were negatively correlated. Treg/Th17 imbalance was closely related to the clinical stage of hepatitis B-associated liver cirrhosis. The Virus load, Treg frequencies and the Treg/Th17 ratio were independent factors predicting decompensated liver cirrhosis from a Cox regression model. The ROC analysis showed that the Treg/Th17 ratio was the best marker for predicting decompensated liver cirrhosis. Conclusions Treg/Th17 imbalance is involved in the pathogenesis of hepatitis B-associated liver cirrhosis and the Treg/Th17 ratio can be used as a potential marker for predicting decompensated liver cirrhosis.

scholarly journals Extended Infusion of β-Lactams for Bloodstream Infection in Patients With Liver Cirrhosis: An Observational Multicenter Study

2019 ◽  
Vol 69 (10) ◽  
pp. 1731-1739 ◽  
Author(s):  
Michele Bartoletti ◽  
Maddalena Giannella ◽  
Russell E Lewis ◽  
Paolo Caraceni ◽  
Sara Tedeschi ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Propensity Score ◽  
Regression Model ◽  
Bloodstream Infection ◽  
Multicenter Study ◽  
Cox Regression ◽  
Intermittent Infusion ◽  
Beta Lactams ◽  
Cirrhotic Patients ◽  
Extended Infusion

Abstract Background We analyzed the impact of continuous/extended infusion (C/EI) vs intermittent infusion of piperacillin-tazobactam (TZP) and carbapenems on 30-day mortality of patients with liver cirrhosis and bloodstream infection (BSI). Methods The BICRHOME study was a prospective, multicenter study that enrolled 312 cirrhotic patients with BSI. In this secondary analysis, we selected patients receiving TZP or carbapenems as adequate empirical treatment. The 30-day mortality of patients receiving C/EI or intermittent infusion of TZP or carbapenems was assessed with Kaplan-Meier curves, Cox-regression model, and estimation of the average treatment effect (ATE) using propensity score matching. Results Overall, 119 patients received TZP or carbapenems as empirical treatment. Patients who received C/EI had a significantly lower mortality rate (16% vs 36%, P = .047). In a Cox-regression model, the administration of C/EI was associated with a significantly lower mortality (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.11–0.936; P = .04) when adjusted for severity of illness and an ATE of 25.6% reduction in 30-day mortality risk (95% CI, 18.9–32.3; P < .0001) estimated with propensity score matching. A significant reduction in 30-day mortality was also observed in the subgroups of patients with sepsis (HR, 0.21; 95% CI, 0.06–0.74), acute-on-chronic liver failure (HR, 0.29; 95% CI, 0.03–0.99), and a model for end-stage liver disease score ≥25 (HR, 0.26; 95% CI, 0.08–0.92). At competing risk analysis, C/EI of beta-lactams was associated with significantly higher rates of hospital discharge (subdistribution hazard [95% CI], 1.62 [1.06–2.47]). Conclusions C/EI of beta-lactams in cirrhotic patients with BSI may improve outcomes and facilitate earlier discharge.

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