scholarly journals Dynamic edge-based biomarker non-invasively predicts hepatocellular carcinoma with hepatitis B virus infection for individual patients based on blood testing

2019 ◽  
Vol 11 (8) ◽  
pp. 665-677 ◽  
Author(s):  
Yiyu Lu ◽  
Zhaoyuan Fang ◽  
Meiyi Li ◽  
Qian Chen ◽  
Tao Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Candidate Genes ◽  
Mononuclear Cells ◽  
Prediction Models ◽  
Non Invasive ◽  
Diagnosis And Prognosis ◽  
B Virus ◽  
Edge Based

Abstract Hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths in Asia and Africa. Developing effective and non-invasive biomarkers of HCC for individual patients remains an urgent task for early diagnosis and convenient monitoring. Analyzing the transcriptomic profiles of peripheral blood mononuclear cells from both healthy donors and patients with chronic HBV infection in different states (i.e. HBV carrier, chronic hepatitis B, cirrhosis, and HCC), we identified a set of 19 candidate genes according to our algorithm of dynamic network biomarkers. These genes can both characterize different stages during HCC progression and identify cirrhosis as the critical transition stage before carcinogenesis. The interaction effects (i.e. co-expressions) of candidate genes were used to build an accurate prediction model: the so-called edge-based biomarker. Considering the convenience and robustness of biomarkers in clinical applications, we performed functional analysis, validated candidate genes in other independent samples of our collected cohort, and finally selected COL5A1, HLA-DQB1, MMP2, and CDK4 to build edge panel as prediction models. We demonstrated that the edge panel had great performance in both diagnosis and prognosis in terms of precision and specificity for HCC, especially for patients with alpha-fetoprotein-negative HCC. Our study not only provides a novel edge-based biomarker for non-invasive and effective diagnosis of HBV-associated HCC to each individual patient but also introduces a new way to integrate the interaction terms of individual molecules for clinical diagnosis and prognosis from the network and dynamics perspectives.

scholarly journals Knowledge-based analyses reveal new candidate genes associated with risk of hepatitis B virus related hepatocellular carcinoma

2020 ◽  
Author(s):  
Deke Jiang(Former Corresponding Author) ◽  
Jiaen Deng ◽  
Changzheng Dong ◽  
Xiaopin Ma ◽  
Qianyi Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Candidate Genes ◽  
Association Analysis ◽  
Susceptibility Loci ◽  
Gene Set ◽  
Knowledge Based ◽  
Gene Sets ◽  
B Virus

Abstract Background: Recent genome-wide association studies (GWASs) have suggested several susceptibility loci of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by statistical analysis at individual single-nucleotide polymorphisms (SNPs). However, these loci only explain a small fraction of HBV-related HCC heritability. In the present study, we aimed to identify additional susceptibility loci of HBV-related HCC using advanced knowledge-based analysis.Methods: We performed knowledge-based analysis (including gene- and gene-set-based association tests) on variant-level association p-values from two existing GWASs of HBV-related HCC. Five different types of gene-sets were collected for the association analysis. A number of SNPs within the gene prioritized by the knowledge-based association tests were selected to replicate genetic associations in an independent sample of 965 cases and 923 controls.Results: The gene-based association analysis detected four genes significantly or suggestively associated with HBV-related HCC risk: SLC39A8, GOLGA8M, SMIM31, and WHAMMP2. The gene-set-based association analysis prioritized two promising gene set for HCC, cell cycle G1/S transition and NOTCH1 intracellular domain regulates transcription. Within the gene sets, three promising candidate genes (CDC45, NCOR1 and KAT2A) were further prioritized for HCC. Among genes of liver-specific expression, multiple genes previously implicated in HCC were also highlighted. However, probably due to small sample size, none of the genes prioritized by the knowledge-based association analyses were successfully replicated in the independent sample. Conclusions: This comprehensive knowledge-based association mining study suggested several promising genes and gene-sets associated with HBV-related HCC risks, which would facilitate follow-up functional studies on the pathogenic mechanism of HCC.

Validation of hepatitis B virus-related hepatocellular carcinoma prediction models in the era of antiviral therapy

Hepatology ◽  
2015 ◽  
Vol 62 (6) ◽  
pp. 1757-1766 ◽  
Author(s):  
Kyu Sik Jung ◽  
Seung Up Kim ◽  
Kijun Song ◽  
Jun Yong Park ◽  
Do Young Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Therapy ◽  
Prediction Models ◽  
B Virus

scholarly journals Identification of Potential Hub Genes Related to Diagnosis and Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma via Integrated Bioinformatics Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Yuqin Tang ◽  
Yongqiang Zhang ◽  
Xun Hu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes ◽  
Diagnosis And Prognosis ◽  
Prognostic Analysis ◽  
B Virus

Hepatocellular carcinoma (HCC) is a common malignant cancer with poor survival outcomes, and hepatitis B virus (HBV) infection is most likely to contribute to HCC. But the molecular mechanism remains obscure. Our study intended to identify the candidate potential hub genes associated with the carcinogenesis of HBV-related HCC (HBV-HCC), which may be helpful in developing novel tumor biomarkers for potential targeted therapies. Four transcriptome datasets (GSE84402, GSE25097, GSE94660, and GSE121248) were used to screen the 309 overlapping differentially expressed genes (DEGs), including 100 upregulated genes and 209 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to explore the biological function of DEGs. A PPI network based on the STRING database was constructed and visualized by the Cytoscape software, consisting of 209 nodes and 1676 edges. Then, we recognized 17 hub genes by CytoHubba plugin, which were further validated on additional three datasets (GSE14520, TCGA-LIHC, and ICGC-LIRI-JP). The diagnostic effectiveness of hub genes was assessed with receiver operating characteristic (ROC) analysis, and all hub genes displayed good performance in discriminating TNM stage I patient samples and normal tissue ones. For prognostic analysis, two prognostic key genes (TOP2A and KIF11) out of the 17 hub genes were screened and used to develop a prognostic signature, which showed good potential for overall survival (OS) stratification of HBV-HCC patients. Gene Set Enrichment Analysis (GSEA) was performed in order to better understand the function of this prognostic gene signature. Finally, the miRNA–mRNA regulatory relationships of all hub genes in human liver were predicted using miRNet. In conclusion, the current study gives further insight on the pathogenesis and carcinogenesis of HBV-HCC, and the identified DEGs provide a promising direction for improving the diagnostic, prognostic, and therapeutic outcomes of HBV-HCC.

Non-Invasive Diagnostic Criteria for Hepatocellular Carcinoma in Hepatitis B Virus-Endemic Areas: Is Cirrhosis Indispensable?

2018 ◽  
Vol 36 (3) ◽  
pp. 228-235 ◽  
Author(s):  
Xiao-wen Huang ◽  
Bing Liao ◽  
Yang Huang ◽  
Jin-yu Liang ◽  
Quan-yuan Shan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Diagnostic Criteria ◽  
Hcv Infection ◽  
Vascular Pattern ◽  
Non Invasive ◽  
B Virus ◽  
Endemic Areas

Aim: To confirm whether cirrhosis is indispensable for the non-invasive diagnostic criteria for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-endemic areas. Methods: Between January 2014 and December 2014, a total of 409 patients with pathologically proven focal liver lesions who underwent contrast-enhanced ultrasound (CEUS) were recruited from our institution. Clinical liver cirrhosis, HBV/HCV infection and HCC-typical vascular pattern of the targeted lesion on CEUS were evaluated. The following 3 criteria were applied to these patients to diagnose HCC: criterion 1, clinical liver cirrhosis and HCC-typical vascular pattern; criterion 2, HBV/HCV infection and HCC-typical vascular pattern; criterion 3, HBV/HCV infection or clinical liver cirrhosis and HCC-typical vascular pattern. Pathological reports were considered the gold standard. Results: A total of 311 patients had confirmed HCC by pathology. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value and area under the ROC curve for criterion 1 were 29.6, 90.8, 44.3, 91.1, 28.9, and 0.60% respectively. For criterion 2, they were 83.3, 74.5, 81.2, 91.2, 58.4, and 0.79%, respectively, and for criterion 3, they were 86.2, 72.5, 82.9, 90.9, 62.3, and 0.79% respectively. Conclusions: In HBV-endemic areas, when using the HBV/HCV infection instead of cirrhosis as the precondition of the non-invasive diagnostic criteria for HCC, we should be aware of the potential false positive. Cirrhosis still plays an important role in the non-invasive diagnostic criteria for HCC because of the high specificity.

scholarly journals Detection and Quantification of Hepatitis B Virus Genomes in Peripheral Blood Mononuclear Cells of Chronic Hepatitis B Virus Infection, Cirrhosis, and Hepatocellular Carcinoma Patients

2022 ◽  
Vol 21 (10) ◽  
Author(s):  
Vahdat Poortahmasebi ◽  
Seyed Moayed Alavian ◽  
Azam Ghaziasadi ◽  
Arezou Azadi ◽  
Mohsen Nasiritoosi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mononuclear Cells ◽  
Hbv Dna ◽  
Peripheral Blood Mononuclear ◽  
Viral Loads ◽  
B Virus ◽  
Blood Mononuclear Cells

Background: Several studies have revealed that the hepatitis B virus (HBV) exists in peripheral blood mononuclear cells (PBMCs). It remains poorly understood whether HBV DNA and covalently closed circular DNA (cccDNA) can emerge in PBMCs of patients with different stages of HBV infection. Objectives: This study aimed to compare the detection of HBV DNA and quantification and presence of cccDNA within PBMC from patients with chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC). Methods: The present study was conducted on 120 participants (30 CHB patients, 30 cirrhosis patients, 30 HCC patients, and 30 healthy controls) from Tehran, Iran. HBV serological markers were tested by enzyme-linked immunosorbent assay (ELISA). PBMCs of all individuals were assayed for HBV DNA detection, quantification, and the presence of cccDNA. Results: Of 90 HBV patients, 58 (64.4%) were positive for HBV DNA in PBMCs. HBV DNA was detected in PBMCs isolated from 13/30 CHB, 20/30 cirrhosis, and 25/30 HCC patients. In addition, 6 (20%) CHB, 13 (43.3%) cirrhosis, and 16 (15.3%) HCC patients were cccDNA positive. The HBV viral loads in serums were statistically higher than the HBV viral loads of PBMCs (P < 0.001). A positive correlation was found between HBV DNA loads in serums and PBMCs of patients. Moreover, HBV DNA quantity of serums and PBMCs showed a significant association in terms of hepatitis B e antigen (HBeAg) status. Conclusions: HBV quantity in PBMCs correlated with serum HBV viral loads. HBV genomes in PBMCs may be a risk factor for HBV disease progression.

scholarly journals Knowledge-based analyses reveal new candidate genes associated with risk of hepatitis B virus related hepatocellular carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Deke Jiang ◽  
Jiaen Deng ◽  
Changzheng Dong ◽  
Xiaopin Ma ◽  
Qianyi Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Candidate Genes ◽  
Knowledge Based ◽  
B Virus

scholarly journals Knowledge-based analyses reveal new candidate genes associated with risk of hepatitis B virus related hepatocellular carcinoma

2020 ◽  
Author(s):  
Deke Jiang ◽  
Jiaen Deng ◽  
Changzheng Dong ◽  
Xiaopin Ma ◽  
Qianyi Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Candidate Genes ◽  
Association Analysis ◽  
Susceptibility Loci ◽  
Gene Set ◽  
Knowledge Based ◽  
Gene Sets ◽  
B Virus

Abstract Background : Recent genome-wide association studies (GWASs) have suggested several susceptibility loci of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by statistical analysis at individual single-nucleotide polymorphisms (SNPs). However, these loci only explain a small fraction of HBV-related HCC heritability. In the present study, we aimed to identify additional susceptibility loci of HBV-related HCC using advanced knowledge-based analysis.Methods: We performed knowledge-based analysis (including gene- and gene-set-based association tests) on variant-level association p-values from two existing GWASs of HBV-related HCC. Five different types of gene-sets were collected for the association analysis. A number of SNPs within the gene prioritized by the knowledge-based association tests were selected to replicate genetic associations in an independent sample of 965 cases and 923 controls.Results: The gene-based association analysis detected four genes significantly or suggestively associated with HBV-related HCC risk: SLC39A8, GOLGA8M, SMIM31, and WHAMMP2. The gene-set-based association analysis prioritized two promising gene set for HCC, cell cycle G1/S transition and NOTCH1 intracellular domain regulates transcription. Within the gene sets, three promising candidate genes (CDC45, NCOR1 and KAT2A) were further prioritized for HCC. Among genes of liver-specific expression, multiple genes previously implicated in HCC were also highlighted. However, probably due to small sample size, none of the genes prioritized by the knowledge-based association analyses are successfully replicated in the independent sample. Conclusions: This comprehensive knowledge-based association mining study suggested several promising genes and gene-sets associated with HBV-related HCC risks, which facilitate follow-up functional studies on the pathogenic mechanism of HCC.

Role of environmental factors in the etiology of hepatocellular carcinoma

2010 ◽  
Vol 151 (28) ◽  
pp. 1132-1136 ◽  
Author(s):  
István Tornai
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Environmental Factors ◽  
Hepatitis B ◽  
Hepatitis A ◽  
Virus Hepatitis ◽  
B Virus

A krónikus vírushepatitisek jelentik ma a legismertebb okokat a hepatocellularis carcinoma (HCC) kialakulásában. A krónikus B- és C-vírus-hepatitis a májrákok körülbelül 40-50%-át okozza. A nyugati típusú társadalmakban a HCC előfordulása folyamatosan növekvő tendenciát mutat. Az alkohol számít a környezeti tényezők közül a legfontosabbnak, bár az alkoholfogyasztás a legtöbb országban csökken. Ez aláhúzza az egyéb környezeti tényezők fontosságát is. Az elfogyasztott alkoholmennyiséggel egyenes arányban növekszik a cirrhosis és a következményes HCC gyakorisága nőkben és férfiakban egyaránt. A kémiai anyagok közül a legismertebb a Kínában és Afrikában elterjedt aflatoxin, amely a gabonaféléket szennyező mycotoxin. Hasonló területeken endémiás, mint a hepatitis B-vírus, együtt szinergista hatást fejtenek ki. A dohányzás is egyértelműen bizonyított hepatocarcinogen hatással rendelkezik. Ez is jelentősen fokozódik, ha alkoholfogyasztással vagy vírushepatitisszel társul. Társadalmilag talán a legfontosabb az elhízás, a következményes nem alkoholos zsírmáj, illetve steatohepatitis és a 2-es típusú cukorbetegség, amelyek prevalenciája egyre fokozódik. Feltehetően ezek állnak a növekvő HCC-gyakoriság hátterében. Az inzulinrezisztencia és az oxidatív stressz képezik a legfontosabb patogenetikai lépéseket a májsejtkárosodásban. További fontos rizikótényező az orális fogamzásgátlók elterjedt használata. Egyes foglalkozások esetén a tartós szervesoldószer-expozíció is növeli a HCC rizikóját. Védelmet jelenthetnek az antioxidánsok, a szelén, a gyógyszerek közül a statinok és a feketekávé-fogyasztás.

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