Identification of key genes and carcinogenic pathways in hepatitis B virus-associated hepatocellular carcinoma through bioinformatics analysis

Abstract Background Hepatitis B virus (HBV) infection is a crucial risk factor for hepatocellular carcinoma (HCC). However, its underlying mechanism remains understudied. Methods Microarray analysis was conducted to compare the genes and miRNAs in liver tissue from HBV-positive and HBV-negative HCC patients. Biological functions of these biomarkers in HBV-related HCC were validated via in vitro and in vivo experiments. Furthermore, we investigated the effect of HBV on the proliferation and migration of tumor cells in HBV-positive HCC tissue. Bioinformatics analysis was then performed to validate the clinical value of the biomarkers in a large HCC cohort. Results We found that a gene, MINPP1 from the glycolytic bypass metabolic pathway, has an important biological function in the development of HBV-positive HCC. MINPP1 is down-regulated in HBV-positive HCC and could inhibit the proliferation and migration of the tumor cells. Meanwhile, miRNA-30b-5p was found to be a stimulator for the proliferation of tumor cell through glycolytic bypass in HBV-positive HCC. More importantly, miRNA-30b-5p could significantly downregulate MINPP1 expression. Metabolic experiments showed that the miRNA-30b-5p/MINPP1 axis is able to accelerate the conversion of glucose to lactate and 2,3-bisphosphoglycerate (2,3-BPG). In the HBV-negative HCC cells, miRNA-30b-5p/MINPP1 could not regulate the glycolytic bypass to promote the tumorigenesis. However, once HBV was introduced into these cells, miRNA-30b-5p/MINPP1 significantly enhanced the proliferation, migration of tumor cells, and promoted the glycolytic bypass. We further revealed that HBV infection promoted the expression of miRNA-30b-5p through the interaction of HBV protein P (HBp) with FOXO3. Bioinformatics analysis on a large cohort dataset showed that high expression of MINPP1 was associated with favorable survival of HBV-positive HCC patients, which could lead to a slower progress of this disease. Conclusion Our study found that the HBp/FOXO3/miRNA-30b-5p/MINPP1 axis contributes to the development of HBV-positive HCC cells through the glycolytic bypass. We also presented miRNA-30b-5p/MINPP1 as a novel biomarker for HBV-positive HCC early diagnosis and a potential pharmaceutical target for antitumor therapy.

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Identification of potential key genes and pathways in hepatitis�B virus‑associated hepatocellular carcinoma by bioinformatics analyses

Oncology Letters ◽

10.3892/ol.2020.11470 ◽

2020 ◽

Author(s):

Xiang Zhang ◽

Lingchen Wang ◽

Yehong Yan

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Bioinformatics Analyses ◽

B Virus ◽

Key Genes

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Bioinformatics analysis of key biomarkers and potential molecular mechanisms in hepatocellular carcinoma induced by hepatitis B virus

Medicine ◽

10.1097/md.0000000000020302 ◽

2020 ◽

Vol 99 (20) ◽

pp. e20302

Author(s):

Zhe Li ◽

Jingyong Xu ◽

Hongyuan Cui ◽

Jinghai Song ◽

Jian Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Molecular Mechanisms ◽

Bioinformatics Analysis ◽

B Virus

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Bioinformatic Identification and Validation of Key Genes and Biological Pathways Involved in Hepatitis B Virus-related Hepatocellular Carcinoma

10.21203/rs.3.rs-106893/v1 ◽

2020 ◽

Author(s):

Guan-Hua Ren ◽

Fan-Biao Mei ◽

Chao-Jun Zhang ◽

Dong-Mei Cai ◽

Long Long ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Hub Genes ◽

Chronic Hepatitis B Virus ◽

B Virus ◽

Key Genes

Abstract Objectives: Hepatocellular carcinoma (HCC) is a common malignant tumor severely scathing human health. As we all know, one of the main risk factors of HCC is chronic hepatitis B virus (HBV) infection, which involved in the oncogenesis of HCC through direct and indirect mechanisms such as inflammatory injury, integration into the host genome and interaction with some special target genes. This study aimed to identify these key genes potentially associated with HBV-related HCC by bioinformatics analyses.Results: Total of 320 DEGs was identified between HBV-related HCC tissue samples and adjacent normal samples. These DGEs were strongly associated with several biological processes, such as retinol metabolism and steroid hormone biosynthesis. A PPI network was constructed and top six hub genes, including CDK1, CCNB1, CDC20, CDKN3, HMMR and MKI67, were determined. GEPIA online tool analysis validated the six key hub genes had the same expression trend as predicted in The Cancer Genome Atlas (TCGA) datasets. The overall survival and disease-free survival reflected that high expression of CDK1, CDC20, HMMR, MKI67 and CCNB1 significantly predicted poor prognosis, whereas CDKN3 expression has no statistical differences in overall survival.Conclusion: The present study identified key genes and pathways involved in HBV-related HCC, which will improve our understanding of the mechanisms underlying the development and recurrence of HCC. The six identified genes might be potential biomarkers for the diagnosis and treatment of HBV-related HCC.

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Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis

Frontiers in Genetics ◽

10.3389/fgene.2020.555537 ◽

2020 ◽

Vol 11 ◽

Author(s):

Xian-Chang Zeng ◽

Lu Zhang ◽

Wen-Jun Liao ◽

Lu Ao ◽

Ze-Man Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Bioinformatics Analysis ◽

B Virus ◽

Screening And Identification ◽

Potential Biomarkers

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Role of environmental factors in the etiology of hepatocellular carcinoma

Orvosi Hetilap ◽

10.1556/oh.2010.28913 ◽

2010 ◽

Vol 151 (28) ◽

pp. 1132-1136 ◽

Cited By ~ 7

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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