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Zeng Z, Liao X, Huang K, Han C, Qin W, Su H, Ye X, Yang C, Zhou X, Wei Y, Mo S, Liu J, Lan C, Huang X, Huang Z, Peng K, Gao Q, Peng T, Zhu G. Outer dynein arm docking complex subunit 2 polymorphism rs7893462 modulates hepatocellular carcinoma susceptibility and can serve as an overall survival biomarker for hepatitis B virus-related hepatocellular carcinoma after hepatectomy: a cohort study with a long-term follow-up. World J Surg Oncol 2023; 21:322. [PMID: 37833735 PMCID: PMC10571289 DOI: 10.1186/s12957-023-03205-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 10/03/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND Genetic variants of outer dynein arm docking complex subunit 2 (ODAD2) have been reported to be closely associated with primary ciliary dyskinesia and colorectal cancer in previous studies, but the association of genetic variants of ODAD2 with hepatocellular carcinoma (HCC) has not been reported. METHODS We enrolled 80 healthy subjects and 468 Guangxi hepatitis B virus (HBV)-related HCC patients in this study. A case-control study method was used to explore the association of different ODAD2-rs7893462 genotypes with hepatocarcinogenesis. A comprehensive survival analysis was used to explore the association of rs7893462 with the prognosis of HBV-related HCC in Guangxi. RESULTS Through a case-control study, we observed that patients carrying the G allele of rs7893462 had a markedly increased susceptibility to hepatocarcinogenesis (odds ratio = 1.712, 95% confidence interval = 1.032-2.839, P = 0.037). We found that there were significant prognosis differences among three different genotypes of rs7893462. Nomogram analysis suggested that the contribution of rs7893462 polymorphisms to the prognosis of HBV-related HCC was second only to the BCLC stage. Stratified survival analysis suggested that the AG genotype of rs7893462 was an independent prognostic risk factor for HBV-related HCC. Joint effect survival analysis also observed that the AG genotype of rs7893462 combined with clinical parameters could significantly identify HBV-related HCC patients with different prognostic outcomes more accurately, and the AG genotype was also observed to be independent of clinical factors in HBV-related HCC survival. CONCLUSION The ODAD2-rs7893462 polymorphisms can be used as an independent prognostic indicator of HBV-related HCC overall survival and are significantly associated with susceptibility to hepatocarcinogenesis.
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Affiliation(s)
- Zhiming Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Ketuan Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Chuangye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Wei Qin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Xinping Ye
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Chengkun Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Xin Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Yongguang Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Shutian Mo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Junqi Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Chenlu Lan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Xinlei Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Zaida Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Kai Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Qiang Gao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
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Shoraka S, Hosseinian SM, Hasibi A, Ghaemi A, Mohebbi SR. The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways. Front Microbiol 2023; 14:1213145. [PMID: 37588887 PMCID: PMC10426804 DOI: 10.3389/fmicb.2023.1213145] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 07/12/2023] [Indexed: 08/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a significant global health issue, with a high prevalence in many regions. There are variations in the etiology of HCC in different regions, but most cases are due to long-term infection with viral hepatitis. Hepatitis B virus (HBV) is responsible for more than 50% of virus-related HCC, which highlights the importance of HBV in pathogenesis of the disease. The development and progression of HBV-related HCC is a complex multistep process that can involve host, viral, and environmental factors. Several studies have suggested that some HBV genome mutations as well as HBV proteins can dysregulate cell signaling pathways involved in the development of HCC. Furthermore, it seems that the pathogenicity, progression of liver diseases, response to treatment and also viral replication are different among HBV mutants. Understanding the relationship between HBV genome variations and host signaling pathway alteration will improve our understanding of the molecular pathogenesis of HBV-related HCC. Furthermore, investigating commonly dysregulated pathways in HBV-related HCC is necessary to discover more specific therapeutic targets and develop more effective strategies for HCC treatment. The objective of this review is to address the role of HBV in the HCC progression and primarily focus on the impacts of HBV genome variations on HCC-related signaling pathways.
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Affiliation(s)
- Shahrzad Shoraka
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Seyed Mahdi Hosseinian
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ayda Hasibi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Ghaemi
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Jaćević V, Dumanović J, Alomar SY, Resanović R, Milovanović Z, Nepovimova E, Wu Q, Franca TCC, Wu W, Kuča K. Research update on aflatoxins toxicity, metabolism, distribution, and detection: A concise overview. Toxicology 2023; 492:153549. [PMID: 37209941 DOI: 10.1016/j.tox.2023.153549] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/07/2023] [Accepted: 05/17/2023] [Indexed: 05/22/2023]
Abstract
Serious health risks associated with the consumption of food products contaminated with aflatoxins (AFs) are worldwide recognized and depend predominantly on consumed AF concentration by diet. A low concentration of aflatoxins in cereals and related food commodities is unavoidable, especially in subtropic and tropic regions. Accordingly, risk assessment guidelines established by regulatory bodies in different countries help in the prevention of aflatoxin intoxication and the protection of public health. By assessing the maximal levels of aflatoxins in food products which are a potential risk to human health, it's possible to establish appropriate risk management strategies. Regarding, a few factors are crucial for making a rational risk management decision, such as toxicological profile, adequate information concerning the exposure duration, availability of routine and some novel analytical techniques, socioeconomic factors, food intake patterns, and maximal allowed levels of each aflatoxin in different food products which may be varied between countries.
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Affiliation(s)
- Vesna Jaćević
- Department for Experimental Pharmacology and Toxicology, National Poison Control Centre, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia; Medical Faculty of the Military Medical Academy, University of Defence, Crnotravska 17, 11000 Belgrade, Serbia; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic.
| | - Jelena Dumanović
- Medical Faculty of the Military Medical Academy, University of Defence, Crnotravska 17, 11000 Belgrade, Serbia; Department of Analytical Chemistry, Faculty of Chemistry, University of Belgrade, 11158 Belgrade, Serbia
| | - Suliman Y Alomar
- King Saud University, College of Science, Zoology Department, Riyadh, 11451, Saudi Arabia
| | - Radmila Resanović
- Faculty of Veterinary Medicine, University of Belgrade, Bulevar Oslobođenja 18, 11000 Belgrade, Serbia
| | - Zoran Milovanović
- Special Police Unit, Ministry of Interior, Trebevićka 12/A, 11 030 Belgrade, Serbia
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
| | - Qinghua Wu
- College of Life Science, Yangtze University, 1 Nanhuan Road, 434023 Jingzhou, Hubei, China; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
| | - Tanos Celmar Costa Franca
- Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense, Military Institute of Engineering, Praça General Tibúrcio 80, Rio de Janeiro, RJ 22290-270, Brazil; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
| | - Wenda Wu
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
| | - Kamil Kuča
- Biomedical Research Center, University Hospital Hradec Kralove, 50005, Hradec Kralove, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, 500 03 Hradec Králové, Czech Republic
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Li F, Duan X, Zhang L, Jiang D, Zhao X, Meng E, Yi R, Liu C, Li Y, Wang JS, Zhao X, Li W, Zhou J. Mycotoxin surveillance on wheats in Shandong province, China, reveals non-negligible probabilistic health risk of chronic gastrointestinal diseases posed by deoxynivalenol. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:71826-71839. [PMID: 35604603 DOI: 10.1007/s11356-022-20812-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 05/10/2022] [Indexed: 06/15/2023]
Abstract
Abnormal climate changes have resulted in over-precipitation in many regions. The occurrence and contamination levels of mycotoxins in crops and cereals have been elevated largely. From 2017 to 2019, we did investigation targeting 15 mycotoxins shown in the wheat samples collected from Shandong, a region suffering over-precipitation in China. We found that deoxynivalenol (DON) was the dominant mycotoxin contaminating wheats, with detection rates 304/340 in 2017 (89.41%), 303/330 in 2018 (91.82%), and 303/340 in 2019 (89.12%). The ranges of DON levels were < 4 to 580 μg/kg in 2017, < 4 to 3070 μg/kg in 2018, and < 4 to 1540 μg/kg in 2019. The exposure levels were highly correlated with local precipitation. Male exposure levels were generally higher than female's, with significant difference found in 2017 (1.89-fold, p = 0.023). Rural exposure levels were higher than that of cities but not statistically significant (1.41-fold, p = 0.13). Estimated daily intake (EDI) and margin of exposure (MoE) approaches revealed that 8 prefecture cities have probabilistically extra adverse health effects (vomiting or diarrhea) cases > 100 patients in 100,000 residents attributable to DON exposure. As a prominent wheat-growing area, Dezhou city reached ~ 300/100,000 extra cases while being considered as a major regional contributor to DON contamination. Our study suggests that more effort should be given to the prevention and control of DON contamination in major wheat-growing areas, particularly during heavy precipitation year. The mechanistic association between DON and chronic intestinal disorder/diseases should be further investigated.
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Affiliation(s)
- Fenghua Li
- Academy of Preventive Medicine, Shandong University, Jinan, 250014, China
- Department of Chemistry and Physics, Center for Food Safety Risk Assessment, Shandong Center for Disease Control and Prevention, Jinan, 250014, China
| | - Xinglan Duan
- School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Liwen Zhang
- Department of Toxicology and Nutrition, School of Public Health, Shandong University, Jinan, 250012, China
| | - Dafeng Jiang
- Academy of Preventive Medicine, Shandong University, Jinan, 250014, China
- Department of Chemistry and Physics, Center for Food Safety Risk Assessment, Shandong Center for Disease Control and Prevention, Jinan, 250014, China
| | - Xianqi Zhao
- School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - En Meng
- School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Ran Yi
- School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Chang Liu
- School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Yirui Li
- School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Jia-Sheng Wang
- Interdisciplinary Toxicology Program and Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA, 30602, USA
| | - Xiulan Zhao
- Department of Toxicology and Nutrition, School of Public Health, Shandong University, Jinan, 250012, China
| | - Wei Li
- Academy of Preventive Medicine, Shandong University, Jinan, 250014, China
- Department of Chemistry and Physics, Center for Food Safety Risk Assessment, Shandong Center for Disease Control and Prevention, Jinan, 250014, China
| | - Jun Zhou
- Department of Toxicology and Nutrition, School of Public Health, Shandong University, Jinan, 250012, China.
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Chen J, Ye Y, Huang D, Pan D, Qiu X, Lei L, Luo X, Li J, Wu K, Xiao S, Liu S, Zeng X. The mediating role of coagulation function on the association of prenatal exposure to aflatoxin B1 and postpartum hemorrhage in Guangxi, China. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:37543-37555. [PMID: 35066843 DOI: 10.1007/s11356-021-18186-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 12/14/2021] [Indexed: 06/14/2023]
Abstract
Pregnant women are vulnerable to certain environmental agents, one of which is aflatoxin. As one of the most popular aflatoxins, Aflatoxin B1 (AFB1) has recently garnered increased attention concerning its potential association between exposure and adverse pregnancy outcomes. The aims of the study were to examine the associations between prenatal exposure to AFB1 and postpartum hemorrhage (PPH), and whether coagulation function has a mediating effect on their relationship. A total of 379 mother-infant pairs were included in the present study. Prenatal serum AFB1 albumin (AFB1-Alb) adduct levels in peripheral venous blood were detected by using an ELISA kit. Multiple linear and logistics regression models were applied to analyze the relationship between AFB1-Alb levels and PPH. We found mothers with high levels of AFB1-Alb adduct levels had significantly increased postpartum blood loss (partial regression coefficient (β) = 50.71, 95% confidence interval (CI) 3.48, 97.95). Mothers with high levels of AFB1-Alb adduct levels also had significantly increased risk of PPH (odds ratio (OR) = 4.81, 95% CI 1.01, 22.98). Moreover, concentrations of AFB1-Alb were positively associated with activated partial thromboplastin time (APTT) while negatively associated with fibrinogen (FIB). One-unit increase in APTT was correlated with a 6.62-ml (95% CI 3.04, 10.20) increase in postpartum blood loss. Mediation analysis suggested that the maternal blood APTT levels had a positive mediating effect in the association between AFB1-Alb adduct levels and postpartum blood loss (β = 0.32, 95% CI 0.04, 0.68). These results indicated that prenatal exposure to AFB1 was associated with increased postpartum blood loss, possibly by interfering with maternal APTT levels.
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Affiliation(s)
- Jiehua Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Ye Ye
- Guangxi Liuzhou Iron & Steel Group Co. Ltd Center for Disease Control and Prevention, Liuzhou, 545002, Guangxi, China
| | - Dongping Huang
- Department of Sanitary Chemistry, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Dongxiang Pan
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Xiaoqiang Qiu
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Lei Lei
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Xingxi Luo
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Jinxiu Li
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Kaili Wu
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Suyang Xiao
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Shun Liu
- Department of Maternal, Child and Adolescent Health, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China.
| | - Xiaoyun Zeng
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China.
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Kumar R. Review on hepatitis B virus precore/core promoter mutations and their correlation with genotypes and liver disease severity. World J Hepatol 2022; 14:708-718. [PMID: 35646275 PMCID: PMC9099108 DOI: 10.4254/wjh.v14.i4.708] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 09/04/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Of 350 million people worldwide are chronically infected with hepatitis B virus (HBV) and are at risk of developing cirrhosis and hepatocellular carcinoma (HCC) later in life. HBV is the most diverse DNA virus, and its genome is composed of four open reading frames: Presurface antigen/surface antigen gene (preS/S), precore/core gene (preC/C), polymerase gene (P), and the X gene (X). HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate. The virus has 10 genotypes (A to J) with different geographical distributions. There are various HBV mutations in the HBV genome, including preC/C mutations, preS/S mutations, P gene mutations, and X gene mutations. The core promoter region plays a vital part in the replication, morphogenesis and pathogenesis of the virus. The precore region also plays a crucial role in viral replication. Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity. preC/C mutations are associated with liver disease progression. Precore mutations stop hepatitis B e antigen (HBeAg) production and basal core promoter mutations downregulate HBeAg production. Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC. The emergence of antiviral-resistant mutations is the main reason for treatment failure. This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity. Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.
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Affiliation(s)
- Rajesh Kumar
- Department of School Education, Haryana Government, Panchkula 134109, Haryana, India
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Huang H, Liao X, Zhu G, Han C, Wang X, Yang C, Zhou X, Liang T, Huang K, Peng T. Acyl-CoA Binding Domain Containing 4 Polymorphism rs4986172 and Expression Can Serve as Overall Survival Biomarkers for Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Hepatectomy. Pharmgenomics Pers Med 2022; 15:277-300. [PMID: 35378899 PMCID: PMC8976523 DOI: 10.2147/pgpm.s349350] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 03/04/2022] [Indexed: 11/23/2022] Open
Abstract
Background The aim of our study was to evaluate the potential of expression and single nucleotide polymorphism of Acyl-CoA binding domain containing 4 (ACBD4) gene as prognosis biomarkers in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after hepatectomy. Methods HBV-related HCC patients from the First Affiliated Hospital of Guangxi Medical University and GSE14520 were included in the current study, as well as The Cancer Genome Atlas (TCGA) HCC verification cohort. Prognostic analysis and multiple functional enrichment analysis methods were used to evaluate the prognostic value and potential biological functions of the ACBD4 gene in HBV-related HCC. Results We found that ACBD4 gene is highly expressed in normal liver tissues and markedly down-regulated in HBV-related HCC tissues. ACBD4 gene was significantly related to overall survival (OS) of HCC in TCGA and GSE14520 cohorts, and patients with low ACBD4 expression were markedly related to poor OS. Rs4986172 was observed as an OS biomarker after hepatectomy in the Guangxi HBV-related HCC cohort. The OS of rs4986172 GG genotype was worse than that of HCC patients with A allele (AA and AG genotypes). Multifunctional enrichment analysis suggested that ACBD4 gene is closely related to the metabolic, peroxisome proliferator-activated receptor and cytochrome P450 pathway. Through connectivity map, we also identified eight compounds that may be used as targeted therapeutic agents for ACBD4 gene in HBV-related HCC; these compounds were scopoletin, alfaxalone, bephenium hydroxynaphthoate, apramycin, 4,5-dianilinophthalimide, DL-thiorphan, aminohippuric acid and quinidine. Immune microenvironment analysis revealed that there were significant differences in immune scores of HBV-related HCC tumor tissues with different ACBD4 expression levels. Conclusion Our study reveals that ACBD4 expression and rs4986172 can be serve as biomarkers of OS in HBV-related HCC patients after hepatectomy.
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Affiliation(s)
- Huasheng Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Chuangye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Xiangkun Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Chengkun Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Xin Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Tianyi Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Ketuan Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Correspondence: Tao Peng; Xiwen Liao, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China, Tel +86-771-5356528, Fax +86-771-5350031, Email ;
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Xue KS, Tang L, Sun G, Wang S, Hu X, Wang JS. Mycotoxin exposure is associated with increased risk of esophageal squamous cell carcinoma in Huaian area, China. BMC Cancer 2019; 19:1218. [PMID: 31842816 PMCID: PMC6916103 DOI: 10.1186/s12885-019-6439-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 12/05/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Consumption of moldy food has previously been identified as a risk factor for esophageal squamous cell carcinoma (ESCC) in high-risk countries; however, what contributing roles these dietary carcinogenic mycotoxins play in the etiology of ESCC are largely unknown. METHODS A mycotoxin biomarker-incorporated, population-based case-control study was performed in Huaian area, Jiangsu Province, one of the two high-risk areas in China. Exposure biomarkers of aflatoxins (AF) and fumonisins (FN) were quantitatively analyzed using HPLC-fluorescence techniques. RESULTS Among the cases (n = 190), the median levels of AF biomarker, serum AFB1-lysine adduct, and FN biomarker, urinary FB1, were 1.77 pg/mg albumin and 176.13 pg/mg creatinine, respectively. Among the controls (n = 380), the median levels of AFB1-lysine adduct and urinary FB1 were 1.49 pg/mg albumin and 56.92 pg/mg creatinine, respectively. These mycotoxin exposure biomarker levels were significantly higher in cases as compared to controls (p < 0.05 and 0.01, respectively). An increased risk to ESCC was associated with exposure to both AFB1 and FB1 (p < 0.001 for both). CONCLUSIONS Mycotoxin exposure, especially to AFB1 and FB1, was associated with the risk of ESCC, and a greater-than-additive interaction between co-exposures to these two mycotoxins may contribute to the increased risk of ESCC in Huaian area, China.
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Affiliation(s)
- Kathy S Xue
- Department of Environmental Health Science, College of Public Health, University of Georgia, 150 Green Street, Athens, GA, 30602, USA
| | - Lili Tang
- Department of Environmental Health Science, College of Public Health, University of Georgia, 150 Green Street, Athens, GA, 30602, USA
| | - Guiju Sun
- Southeast University School of Public Health, Nanjing, Jiangsu, China
| | - Shaokang Wang
- Southeast University School of Public Health, Nanjing, Jiangsu, China
| | - Xu Hu
- Huaian District Center for Disease Control and Prevention, Huaian, Jiangsu, China
| | - Jia-Sheng Wang
- Department of Environmental Health Science, College of Public Health, University of Georgia, 150 Green Street, Athens, GA, 30602, USA.
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9
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Next generation sequencing identifies baseline viral mutants associated with treatment response to pegylated interferon in HBeAg-positive chronic hepatitis B. Virus Genes 2019; 55:610-618. [PMID: 31359359 DOI: 10.1007/s11262-019-01689-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 07/18/2019] [Indexed: 12/27/2022]
Abstract
Current data of hepatitis B virus (HBV) variants associated with treatment outcome identified by next generation sequencing (NGS) are limited. This study was aimed at determining the role of baseline sequence variations in the enhancer II (EnhII), basal core promotor (BCP) and pre-core (PC) regions of HBV genotype C in patients treated with pegylated interferon (PEG-IFN). Patients with HBeAg-positive chronic hepatitis B (CHB) treated with 48-week PEG-IFN were enrolled. Combined response (CR) at week 96 was defined by HBeAg seroconversion plus HBV DNA < 2000 IU/mL and HBsAg < 1000 IU/mL. Pre-treatment viral mutations were characterized by Sanger sequencing and NGS (Miseq Illumina platform). Among 47 patients (32 male, mean age 32.4 years), CR was achieved in 12 (25.5%) individuals. Overall, NGS was superior to Sanger sequencing in detecting mutations (61.7% vs. 38.3%, P < 0.001). Based on NGS, the prevalence of T1753V (T1753C/A/G) and A1762T/G1764A variants were significantly lower in responders compared to non-responders (8.3% vs. 51.4%, P = 0.009 and 33.3% vs. 68.6%, P = 0.032, respectively). No significant difference between groups was found regarding C1653T and G1896A mutants. The absence of T1753V and A1762T/G1764A mutations were factors associated with CR (OR 11.65, 95%CI 1.36-100.16, P = 0.025, and OR 4.36, 95%CI 1.08-17.63, P = 0.039, respectively). The existence of pre-treatment T1753V, A1762T/G1764A mutations and their combination yielded negative predictive values of 94.7%, 85.7% and 93.8%, respectively. The presence of HBV mutants in the BCP region determined by NGS at baseline was associated with poor treatment outcome in patients with HBeAg-positive CHB receiving PEG-IFN.
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10
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Zhang W, Chen J, Liu L, Wang L, Liu J, Su D. Prognostic value of preoperative computed tomography in HBV-related hepatocellular carcinoma patients after curative resection. Onco Targets Ther 2019; 12:3791-3804. [PMID: 31190879 PMCID: PMC6529036 DOI: 10.2147/ott.s199136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 03/05/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Preoperative treatments are considered for patients with worse outcome to improve overall survival and reduce tumor relapse. This study developed a prognostic risk estimation for patients with hepatitis B virus (HBV)-related solitary hepatocellular carcinoma after curative resection, including preoperative computed tomography (CT) signatures. Methods: Preoperative multiphasic CTs for 166 patients with operable HCC were performed in our hospital from 15 November 2013 through 15 May 2015. Follow-up information, until 5 June 2017, included: CT, pathological and clinical characteristics, and recurrence and metastases of HCC confirmed by pathological or radiological diagnosis. The parameters were analyzed by the Kaplan-Meier method and Cox proportional hazards regression analysis. Results: In multivariate analyses, overall survival was not significantly associated with any of the analyzed prognostic risk factors, but did show that the following were significant prognostic risk factors for disease-free survival: larger tumor size, positive radiogenomic venous invasion, non-smooth tumor margin, and histological microvascular invasion. These were all incorporated into the nomogram. The calibration curves for predicting the probability of disease-free survival between the nomogram and actual observation showed good conformity. Conclusion: In patients with HBV-related HCC, CT signatures were a noninvasive significant indicator of disease-free survival. Thus, consideration of CT signatures may optimize preoperative treatment strategies for the individual patient.
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Affiliation(s)
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
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11
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Díaz de León-Martínez L, Díaz-Barriga F, Barbier O, Ortíz DLG, Ortega-Romero M, Pérez-Vázquez F, Flores-Ramírez R. Evaluation of emerging biomarkers of renal damage and exposure to aflatoxin-B 1 in Mexican indigenous women: a pilot study. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2019; 26:12205-12216. [PMID: 30835068 DOI: 10.1007/s11356-019-04634-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 02/19/2019] [Indexed: 05/18/2023]
Abstract
Aflatoxins (AFs) are mycotoxins produced by Aspergillus parasiticus and Aspergillus flavus which frequently contaminate maize. These compounds are considered toxic, especially AFB1 which has been classified as a human carcinogen, due to its relationship with the generation of hepatocellular carcinoma. Studies in vivo, in animal models, prove that chronic consumption of AFB1 has an association with renal adverse effects, but evidence in humans is scarce. Therefore, the main objective of this research was to conduct a pilot study to evaluate the correlation between exposure to AFB1 and early-stage renal damage in indigenous women of San Luis Potosí, Mexico. Exposure to AFB1 was measured through the biomarker AFB1-lysine and renal damage through kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin-C (Cys-C). AFB1-Lys was measured by HPLC-FLD. The method was validated with a correlation coefficient of 0.99 and limit of detection and quantification of 3.5 and 4.7 pg mL-1, respectively. Levels of NGAL, KIM-1, and Cys-C were determined (median (P25-P75), 5.96 (3.16-15.91), 0.137 (0.137-0.281), and 18.49 (5.76-29.57) ng mL-1, respectively). Additionally, glomerular filtration rate (GFR) (83.3 (59.8-107.4) mL/min/1.73 m2) and serum creatinine (SCr) (0.88 (0.72-1.22) mg dL-1) were obtained. The median concentrations for AFB1-Lys were 2.08 (1.89-5.8) pg mg-1 of albumin. Statistically significant correlations between AFB1-Lys/KIM-1 (Rho = 0.498, p = 0.007) and AFB1/Cys-C (Rho = 0.431, p = 0.014) were found. Our results indicate that women are exposed to AFB1, due to the fact that the AFB1-Lys biomarker was found in a high percentage of the study population (83%). In addition, the results of exposure to AFB1 show a strong significant correlation between KIM-1 and Cys-C that may indicate the toxic renal effect. These results are alarming because of the high toxicity of this compound and require adequate intervention to reduce AFB1 exposure in these populations.
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Affiliation(s)
- Lorena Díaz de León-Martínez
- Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Avenida Sierra Leona No. 550, Colonia Lomas Segunda Sección, 78210, San Luis Potosí, SLP, Mexico
| | - Fernando Díaz-Barriga
- Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Avenida Sierra Leona No. 550, Colonia Lomas Segunda Sección, 78210, San Luis Potosí, SLP, Mexico
| | - Olivier Barbier
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados-Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City, Mexico
| | - Dora Linda Guzmán Ortíz
- Departamento de Biotecnología y Bioquímica Centro de Investigación de Estudios Avanzados del -Instituto Politécnico Nacional (CINVESTAV-IPN), Campus Guanajuato, Irapuato, Mexico
| | - Manolo Ortega-Romero
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados-Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City, Mexico
| | - Francisco Pérez-Vázquez
- Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Avenida Sierra Leona No. 550, Colonia Lomas Segunda Sección, 78210, San Luis Potosí, SLP, Mexico
| | - Rogelio Flores-Ramírez
- CONACYT Research Fellow, Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Avenida Sierra Leona No. 550, Colonia Lomas Segunda Sección, 78210, San Luis Potosí, SLP, Mexico.
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12
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Liao X, Han C, Qin W, Liu X, Yu L, Zhu G, Yu T, Lu S, Su H, Liu Z, Chen Z, Yang C, Huang K, Liu Z, Liang Y, Huang J, Dong J, Li L, Qin X, Ye X, Xiao K, Peng M, Peng T. PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy. Oncotarget 2018; 8:29202-29219. [PMID: 28418898 PMCID: PMC5438724 DOI: 10.18632/oncotarget.16346] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 02/22/2017] [Indexed: 12/17/2022] Open
Abstract
Polymorphisms in the phospholipase C epsilon (PLCE) 1 gene play a crucial role in the development and progression of several types of cancer. The present study investigated the prognostic significance of PLCE1 gene polymorphisms and expression combined with serum α-fetoprotein (AFP) level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Single nucleotide polymorphisms were genotyped by sequencing DNA isolated from surgically resected tumor samples of 421 HBV-related HCC patients, and expression profiles were generated based on the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes (Ars2274223Crs3765524; Grs2274223Trs3765524) with AFP level stratified at 20 ng/ml showed a significant association with overall survival(OS) of HBV-related HCC patients(log-rank P=0.0003). Patients with AC and GT haplotypes with AFP level ≥ 20 ng/ml had an increased risk of death as compared to those with the AC haplotype and AFP level < 20 ng/ml (adjusted P=0.029 and 0.041, respectively). Patients with the GT haplotype and AFP level < 20 ng/ml also had an increased risk of death, although with a non-significant P value (adjusted P=0.092). Joint-effects analysis of PLCE1 mRNA expression with serum AFP level stratified at 300 ng/ml was significantly associated with HBV-related HCC recurrence and OS. Our results demonstrate that PLCE1 haplotypes (including rs2274223 and rs3765524) and expression combined with serum AFP level may predict postoperative outcome of HBV-related HCC patients.
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Affiliation(s)
- Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Chuangye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Wei Qin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Xiaoguang Liu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong Province, China
| | - Long Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan Province, China
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Tingdong Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Sicong Lu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Zhen Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Zhiwei Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Chengkun Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Ketuan Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Zhengtao Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Yu Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Jianlu Huang
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Province, China
| | - Jiahong Dong
- Department of Hepato-Biliary-Pancreatic Surgery, Beijing Tsinghua Changgung Hospital, Beijing, 102218, China
| | - Lequn Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Xue Qin
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China
| | - Xinping Ye
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Kaiyin Xiao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Minhao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
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13
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Liu WC, Wu IC, Lee YC, Lin CP, Cheng JH, Lin YJ, Yen CJ, Cheng PN, Li PF, Cheng YT, Cheng PW, Sun KT, Yan SL, Lin JJ, Yang JC, Chang KC, Ho CH, Tseng VS, Chang BCH, Wu JC, Chang TT. Hepatocellular carcinoma-associated single-nucleotide variants and deletions identified by the use of genome-wide high-throughput analysis of hepatitis B virus. J Pathol 2017; 243:176-192. [PMID: 28696069 DOI: 10.1002/path.4938] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Revised: 05/31/2017] [Accepted: 07/04/2017] [Indexed: 12/26/2022]
Abstract
This study investigated hepatitis B virus (HBV) single-nucleotide variants (SNVs) and deletion mutations linked with hepatocellular carcinoma (HCC). Ninety-three HCC patients and 108 non-HCC patients were enrolled for HBV genome-wide next-generation sequencing (NGS) analysis. A systematic literature review and a meta-analysis were performed to validate NGS-defined HCC-associated SNVs and deletions. The experimental results identified 60 NGS-defined HCC-associated SNVs, including 41 novel SNVs, and their pathogenic frequencies. Each SNV was specific for either genotype B (n = 24) or genotype C (n = 34), except for nt53C, which was present in both genotypes. The pathogenic frequencies of these HCC-associated SNVs showed a distinct U-shaped distribution pattern. According to the meta-analysis and literature review, 167 HBV variants from 109 publications were categorized into four levels (A-D) of supporting evidence that they are associated with HCC. The proportion of NGS-defined HCC-associated SNVs among these HBV variants declined significantly from 75% of 12 HCC-associated variants by meta-analysis (Level A) to 0% of 10 HCC-unassociated variants by meta-analysis (Level D) (P < 0.0001). PreS deletions were significantly associated with HCC, in terms of deletion index, for both genotypes B (P = 0.030) and C (P = 0.049). For genotype C, preS deletions involving a specific fragment (nt2977-3013) were significantly associated with HCC (HCC versus non-HCC, 6/34 versus 0/32, P = 0.025). Meta-analysis of preS deletions showed significant association with HCC (summary odds ratio 3.0; 95% confidence interval 2.3-3.9). Transfection of Huh7 cells showed that all of the five novel NGS-defined HCC-associated SNVs in the small surface region influenced hepatocarcinogenesis pathways, including endoplasmic reticulum-stress and DNA repair systems, as shown by microarray, real-time polymerase chain reaction and western blot analysis. Their carcinogenic mechanisms are worthy of further research. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Affiliation(s)
- Wen-Chun Liu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.,Infectious Disease and Signalling Research Centre, National Cheng Kung University, Tainan, Taiwan, ROC
| | - I-Chin Wu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.,Infectious Disease and Signalling Research Centre, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Yen-Chien Lee
- Department of Oncology, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan, ROC.,Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
| | | | - Ji-Hong Cheng
- Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan, ROC
| | - Chia-Jui Yen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.,Infectious Disease and Signalling Research Centre, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.,Infectious Disease and Signalling Research Centre, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Pei-Fu Li
- Institute of Medical Informatics, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Yi-Ting Cheng
- Institute of Medical Informatics, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Pei-Wen Cheng
- Department of Information and Learning Technology, Science and Engineering College, National University of Tainan, Tainan, Taiwan, ROC
| | - Koun-Tem Sun
- Department of Information and Learning Technology, Science and Engineering College, National University of Tainan, Tainan, Taiwan, ROC
| | - Shu-Ling Yan
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Jia-Jhen Lin
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Jui-Chu Yang
- Human Biobank, Research Centre of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC
| | - Kung-Chao Chang
- Human Biobank, Research Centre of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, ROC
| | - Cheng-Hsun Ho
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.,Infectious Disease and Signalling Research Centre, National Cheng Kung University, Tainan, Taiwan, ROC
| | - Vincent S Tseng
- Department of Computer Science, National Chiao Tung University, Hsinchu, Taiwan, ROC
| | | | - Jaw-Ching Wu
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.,Translational Research Division, Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.,Infectious Disease and Signalling Research Centre, National Cheng Kung University, Tainan, Taiwan, ROC
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14
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Zhu G, Liao X, Han C, Liu X, Yu L, Qin W, Lu S, Su H, Chen Z, Liu Z, Liang Y, Huang J, Yu T, Yang C, Huang K, Shang L, Ye X, Li L, Qin X, Xiao K, Peng M, Peng T. ALDH1L1 variant rs2276724 and mRNA expression predict post-operative clinical outcomes and are associated with TP53 expression in HBV-related hepatocellular carcinoma. Oncol Rep 2017; 38:1451-1463. [PMID: 28714006 PMCID: PMC5549030 DOI: 10.3892/or.2017.5822] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 06/29/2017] [Indexed: 12/24/2022] Open
Abstract
Aldehyde dehydrogenase 1 family member L1 (ALDH1L1) is downregulated in hepatocellular carcinoma (HCC) tumors, and its decreased expression is associated with the poor prognosis of HCC patients. We, therefore, evaluated the effect of single nucleotide polymorphisms (SNPs) of ALDH1L1, and its mRNA expression on the survival of hepatitis B virus (HBV)-related HCC patients and the association with tumor protein p53 (TP53) expression. ALDH1L1 SNPs in 415 HBV-related HCC patients were genotyped via direct sequencing. Expression profile chip datasets and survival information were obtained from GSE14520. The C allele (CT/CC) carriers of rs2276724 were significantly associated with a favorable prognosis [adjusted P=0.040; adjusted hazard ratio (HR)=0.725; 95% confidence interval (CI)=0.533–0.986]. Joint-effect analyses suggested that the CT/CC genotype of rs2276724 in TP53-negative patients was significantly associated with a decreased risk of death, compared to the TT genotype of rs2276724 in TP53-positive patients (adjusted P=0.037; adjusted HR=0.621; 95% CI=0.396–0.973). Furthermore, low expression of ALDH1L1 predicted a poor prognosis for the HBV-related HCC patients (adjusted P=0.04 for disease-free survival; adjusted P=0.001 for overall survival). Patients with high ALDH1L1 expression and low TP53 expression were significantly associated with a decreased risk of recurrence and death, and patients with a high TP53 expression were also significantly associated with a decreased risk of death in HBV-related HCC, compared with low ALDH1L1 and low TP53 expression. Our results suggest that ALDH1L1 may be a biomarker for predicting postoperative clinical outcomes. Moreover, ALDH1L1-rs2276724 and mRNA expression were associated with TP53 expression in HBV-related HCC patients.
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Affiliation(s)
- Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Chuangye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Xiaoguang Liu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
| | - Long Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
| | - Wei Qin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Sicong Lu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Zhiwei Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Zhengtao Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Yu Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Jianlu Huang
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530031, P.R. China
| | - Tingdong Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Chengkun Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Ketuan Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Liming Shang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Xinping Ye
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Lequn Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Xue Qin
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Kaiyin Xiao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Minhao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
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15
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Abstract
BACKGROUND More and more studies focus on the relationship between hepatitis B virus (HBV) basal core promoter/precore (BCP/PC) mutations, but it remains controvercial, we conducted a meta-analysis to investigate the features of hepatitis B virus basal core promoter/precore mutations on the progression of hepatocellular carcinoma (HCC). METHODS A comprehensive search was conducted for articles published between January 1, 2005 and December 31, 2015 using the following databases: PubMed, Embase, Cochrane Library, Wanfang, and China National Knowledge Infrastructure. Medical subject heading terms were prioritized in setting the search strategy. Search terms included ("hepatitis B virus"), ("mutation or mutations or mutant"), and ("hepatocellular carcinoma" or "liver cancer" or hepatoma). A meta-analysis of pooled results from case-control studies examined the association between mutations G1896A, A1762T, G1764A, and A1762T/G1764A and the risk of HCC. RESULTS We included 29 articles for analysis and found that G1896A (summary odds ratios [OR] = 2.04, 95% confidence interval [CI] = 1.41-2.95), A1762T (summary OR = 3.96, 95% CI = 1.98-7.92), G1764A (summary OR = 3.48, 95% CI = 1.99-6.09), and A1762T/G1764A (summary OR = 3.96, 95% CI = 2.77-5.65) are each associated with a statistically significant increase in the risk of HCC. CONCLUSION In summary, we found that G1896A, A1762T, G1764A, and A1762T/G1764A are associated with an increased risk of HCC.
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Affiliation(s)
- Fangfang Wei
- Department of Infectious Disease, Guangdong Second Provincial General Hospital
| | | | - Maoyin Li
- Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Maosheng Wu
- Department of Infectious Disease, Guangdong Second Provincial General Hospital
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Xue KS, Cai W, Tang L, Wang JS. Aflatoxin B1-lysine adduct in dried blood spot samples of animals and humans. Food Chem Toxicol 2016; 98:210-219. [DOI: 10.1016/j.fct.2016.11.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 10/30/2016] [Accepted: 11/01/2016] [Indexed: 11/16/2022]
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Kim H, Lee SA, Kim BJ. X region mutations of hepatitis B virus related to clinical severity. World J Gastroenterol 2016; 22:5467-5478. [PMID: 27350725 PMCID: PMC4917607 DOI: 10.3748/wjg.v22.i24.5467] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 05/17/2016] [Accepted: 06/02/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection remains a major health problem, with more than 240 million people chronically infected worldwide and potentially 650000 deaths per year due to advanced liver diseases including liver cirrhosis and hepatocellular carcinoma (HCC). HBV-X protein (HBx) contributes to the biology and pathogenesis of HBV via stimulating virus replication or altering host gene expression related to HCC. The HBV X region contains only 465 bp encoding the 16.5 kDa HBx protein, which also contains several critical cis-elements such as enhancer II, the core promoter and the microRNA-binding region. Thus, mutations in this region may affect not only the HBx open reading frame but also the overlapped cis-elements. Recently, several types of HBx mutations significantly associated with clinical severity have been described, although the functional mechanism in most of these cases remains unsolved. This review article will mainly focus on the HBx mutations proven to be significantly related to clinical severity via epidemiological studies.
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Yang Z, Zhuang L, Lu Y, Xu Q, Tang B, Chen X. Naturally occurring basal core promoter A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma: a meta-analysis. Oncotarget 2016; 7:12525-12536. [PMID: 26848866 PMCID: PMC4914302 DOI: 10.18632/oncotarget.7123] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 01/23/2016] [Indexed: 02/05/2023] Open
Abstract
Basal core promoter (BCP) A1762T/G1764A dual mutations in hepatocarcinogenesis remain controversial. Published studies up to June 1, 2015 investigating the frequency of A1762T/G1764A dual mutations from chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma (HCC), were systematically identified. A total of 10,240 patients with chronic HBV infection, including 3729 HCC cases, were included in 52 identified studies. HCC patients had a higher frequency of BCP A1762T/G1764A dual mutations compared with asymptomatic HBsAg carriers (ASC) and patients with chronic hepatitis B (CHB) and liver cirrhosis (LC) (OR = 5.59, P < 0.00001; OR = 2.87, P < 0.00001; OR = 1.55, P = 0.02, respectively). No statistically significant difference was observed in the frequency of A1762T/G1764A dual mutations in cirrhotic HCC versus non-cirrhotic HCC patients (OR = 2.06, P = 0.05). Chronic HBV-infected patients and HCC patients with genotype B had a significantly lower risk of A1762T/G1764A dual mutations compared with patients with genotype C (OR = 0.30, P < 0.0001 and OR = 0.34, P = 0.04, respectively). In HBV genotype C subjects, A1762T/G1764A dual mutations contributed to significantly higher risk for HCC developing compared with non-mutation ones (OR = 3.47, P < 0.00001). In conclusion, A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma, particularly in an HBV genotype C population, even without progression to cirrhosis.
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Affiliation(s)
- Zongguo Yang
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Liping Zhuang
- Fudan University Shanghai Cancer Center, Shanghai, China
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Yunfei Lu
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Qingnian Xu
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Bozong Tang
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xiaorong Chen
- Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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19
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Sun X, Jin Z, Song X, Wang J, Li Y, Qian X, zhang Y, Yin Y. Evaluation of KIF23 variant 1 expression and relevance as a novel prognostic factor in patients with hepatocellular carcinoma. BMC Cancer 2015; 15:961. [PMID: 26674738 PMCID: PMC4682286 DOI: 10.1186/s12885-015-1987-1] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Accepted: 12/08/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND KIF23 (kinesin family member 23) is a kinesin-like motor protein and plays an important role in cytokinesis. In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that KIF23 was upregulated in HCC tissues. At present, much less is known about its expression and functions in tumor cells. In this work, we aimed to investigate the expression of KIF23 in HCC and the correlation between its expression and clinical features. METHODS Total RNA was extracted from 16 HCC and paired adjacent non-cancerous tissues. The expressions of the two KIF23 splice variants (KIF23 V1 and KIF23 V2) in normal and HCC tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Polyclonal antibody specific to KIF23 V1 was prepared, and the specificity of the antibody was confirmed by siRNA knockdown and Western blotting experiments. KIF23 protein expression in HCC was examined by immunohistochemistry staining with anti-KIF23 V1 or anti-KIF23 (commercially available for recognizing both KIF23 V1 and V2) antibodies, respectively. Univariate and Multivariate Cox regression analyses were used to determine the correlation between KIF23 protein expression and overall survival of HCC patients. RESULTS The two splicing variants of KIF23 mRNA were not detected in normal liver tissue by RT-PCR, but they were aberrantly expressed in HCC tissues. Immunohistochemistry staining with anti-KIF23 V1 antibody revealed that KIF23 V1 was mainly distributed in the nucleus, whereas the positive staining signals were predominantly in the cytoplasm when using anti-KIF23 antibody, suggesting that KIF23 V2 might localize in the cytoplasm of HCC cells. KIF23 V1 protein was detected in 57.6% (83/144) HCC patients and the mean H-score was 42, while KIF23 V2 was detected in 94.4% (135/143) HCC samples and the mean H-score was 68. Follow-up study showed that HCC patients with expression of KIF23 V1 had a longer 5-year survival (p=0.0052), however, expression of KIF23 V2 protein did not associate with 3- and 5-year survival. CONCLUSION In this study we show for the first time that KIF23 V1 and V2 have different localizations in HCC cells. Furthermore, KIF23 V1 protein expression might be a marker of longer overall survival in HCC patients.
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Affiliation(s)
- Xiaotong Sun
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
| | - Zhongtian Jin
- Center of Hepatobiliary Surgery, People's Hospital, Peking University Health Science Center, Beijing, China.
| | - Xiao Song
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
| | - Jingjing Wang
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
| | - Yan Li
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
| | - Xiaoping Qian
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
| | - Yu zhang
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
| | - Yanhui Yin
- Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
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20
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Alcohol consumption and liver cancer risk: a meta-analysis. Cancer Causes Control 2015; 26:1205-31. [PMID: 26134046 DOI: 10.1007/s10552-015-0615-3] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 06/09/2015] [Indexed: 02/07/2023]
Abstract
PURPOSE Alcohol is a confirmed risk factor of liver cancer. Yet, its dose-response function and synergistic effects with other risk factors remain unclear. METHODS We performed a meta-analysis on publications up to May 2014. A total of 112 publications were identified. The meta-relative risk (mRR) and the dose-response trend were calculated. Tests for heterogeneity, publication bias, and sensitivity analyses were performed. The synergy index (SI) was recorded or calculated, whenever possible. RESULTS Compared to individuals who never drank or drank at very low frequencies, the mRR for ever drinkers was 1.29 (95% confidence interval, CI 1.16-1.42) and 1.46 (95% CI 1.27-1.65) for case-control studies, and 1.07 (95% CI 0.87-1.27) for cohort studies. Being a current drinker was associated with an increased liver cancer risk in case-control studies (mRR = 1.55, 95% CI 0.38-2.73), but not in cohort studies (mRR = 0.86, 95% CI 0.74-0.97). The dose-response relation between alcohol and liver cancer was apparent with RR = 1.08 (95% CI 1.04-1.11) for 12 g/day (~1 drink), 1.54 (95% CI 1.36-1.74) for 50 g/day, 2.14 (95% CI 1.74-2.62) for 75 g/day, 3.21 (95% CI 2.34-4.40) for 100 g/day, and 5.20 (95% CI 3.25-8.29) for 125 g/day of alcohol consumption. There were synergistic effects of alcohol consumption with hepatitis (S = 2.14, 95% CI 1.31-2.98) and with diabetes (S = 3.57, 95% CI 2.29-4.84) on the risk of liver cancer, although this may be subject to publication bias. CONCLUSION Overall, one alcoholic drink per day (~12 g/day) may be associated with a 1.1 times higher liver cancer risk. Further studies on the synergistic effects of alcohol consumption and other major risk factors are warranted.
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Li G, Yuan L, Liu D, Liu J. Upregulation of Leucine Zipper Protein mRNA in Hepatocellular Carcinoma Associated With Poor Prognosis. Technol Cancer Res Treat 2015; 15:517-22. [PMID: 26031464 DOI: 10.1177/1533034615587432] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2014] [Accepted: 04/23/2015] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Leucine zipper protein (LUZP) plays key roles in development. Overexpression of LUZP was documented in several types of solid tumors. In this study, expression of LUZP messenger RNA (LUZP mRNA) in human hepatocellular carcinoma (HCC) was examined, and the correlations of LUZP mRNA level with patients' characteristics and prognosis were also investigated. METHODS Total RNA was extracted from HCC and paired noncancerous liver tissues of 77 patients. Expression of LUZP mRNA in the tissues was determined by real-time quantitative reverse transcriptase polymerase chain reaction. Using average LUZP mRNA level in noncancerous liver tissues as the cutoff, patients with HCC were categorized into high-expression group and low-expression group. Correlations of LUZP mRNA with clinical parameters were analyzed. Overall survival of the patients in the 2 groups was analyzed by Kaplan-Meier method. RESULTS The LUZP mRNA level was significantly higher in HCC samples than in the noncancerous liver tissues (1.87 ± 0.11 vs 0.58 ± 0.05, P < .01). Significant differences were found between the 2 groups in terms of portal vein invasion, Tumor Lymph Node Metastasis (TNM) stage, and recurrence of HCC. The current study failed to find significant differences between the 2 groups in clinical characteristics such as age, gender, lymph node metastasis, hepatitis B virus infection, family HCC history, and alcohol intake. Overall survival in high-expression group was 12 months while that in the low-expression group was 34 months (P = .03). CONCLUSION The LUZP mRNA is a prognostic indicator in HCC, and overexpression is associated with poor prognosis in patients with HCC.
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Affiliation(s)
- Guangbing Li
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People's Republic of China
| | - Li Yuan
- Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People's Republic of China
| | - Dejie Liu
- Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China
| | - Jun Liu
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People's Republic of China
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Kucukcakan B, Hayrulai-Musliu Z. Challenging Role of Dietary Aflatoxin B1 Exposure and Hepatitis B Infection on Risk of Hepatocellular Carcinoma. Open Access Maced J Med Sci 2015; 3:363-9. [PMID: 27275251 PMCID: PMC4877883 DOI: 10.3889/oamjms.2015.032] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2014] [Revised: 02/21/2015] [Accepted: 02/24/2015] [Indexed: 12/22/2022] Open
Abstract
Aflatoxins (AFT) are poisonous substances which are classified in Group 1 carcinogenic agents to humans by International Agency for Research on Cancer (IARC). AFT can occur naturally in food commodities (maize, corn, rice) as a result of fungal contamination in hot and humid environments. In the food, toxin contamination can remain during manufacturing and long after fungi have stopped being biologically active. Aflatoxin B1 (AFB1) is the most dominant and potent agent from all AFT. In developing countries, high exposure to AFB1 can cause chronic toxicity and usually increases the incidence of Hepatocellular Carcinoma (HCC). However, in these regions hepatitis B is the most common risk factor for HCC cases. Many researches were aimed to enlighten the mechanism and the role of two etiological agents on risk of HCC, but the obtained data was conflicting with each other. It was uncertain that the indicators/biomarkers might be the contribution of the carcinogenic status of the patient; and, the biomarker samples from the subject may only reflect the recent effects of the toxin exposure after consumption of AFB1 contaminated commodities. The studies were facing with the errors of methods which were un-fit to enlighten the possible interaction between Hepatitis B and AFB1 on contribution to HCC. It was pivotal to understand the effect of each risk factor in order to prevent and improve public health in poor and undeveloped regions. Although some of the studies evaluate AFB1 alone as a considerable factor on HCC risk, according to this review it was concluded vice versa. This study was aimed to clarify the main etiological agent of HCC where AFB1 and HBV are endangering public health. In additionally, the purpose was to enlighten the possible synergistic effect between these two factors among HCC pathogenesis. Hence forth, appropriate and right applications could be conducted in undeveloped countries in order to protect public health.
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Affiliation(s)
- Basak Kucukcakan
- Ss. Cyril and Methodius University of Skopje, Faculty of Veterinary Medicine, Department of Food Safety, Skopje, Republic of Macedonia
| | - Zehra Hayrulai-Musliu
- Ss. Cyril and Methodius University of Skopje, Faculty of Veterinary Medicine, Department of Food Safety, Skopje, Republic of Macedonia
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23
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Wang Y, Xue BY, Liu L, Zhu Z, Xu X, Zhang H, Pu X, Liu X. Poly-linker primer system for detection of single nucleotide polymorphisms and its application in genotyping hepatitis B virus. Acta Biochim Biophys Sin (Shanghai) 2015; 47:139-41. [PMID: 25520176 DOI: 10.1093/abbs/gmu115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Yongzhong Wang
- Laboratory Centre, The Third People's Hospital of Changzhou, Changzhou 213001, China
| | - Bo-Yu Xue
- University of Nanjing Traditional Chinese Medicine, Nanjing 210023, China
| | - Longgen Liu
- University of Nanjing Traditional Chinese Medicine, Nanjing 210023, China
| | - Zhen Zhu
- Laboratory Centre, The Third People's Hospital of Changzhou, Changzhou 213001, China
| | - Xin Xu
- Laboratory Centre, The Third People's Hospital of Changzhou, Changzhou 213001, China
| | - Hongyu Zhang
- Laboratory Centre, The Third People's Hospital of Changzhou, Changzhou 213001, China
| | - Xiangke Pu
- Laboratory Centre, The Third People's Hospital of Changzhou, Changzhou 213001, China
| | - Xiaoqin Liu
- Laboratory Centre, The Third People's Hospital of Changzhou, Changzhou 213001, China
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24
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Sass DC, Jager AV, Tonin FG, Rosim RE, Constantino MG, Oliveira CAF. Synthesis and purification of the aflatoxin B1-lysine adduct. TOXIN REV 2014. [DOI: 10.3109/15569543.2014.994132] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Lai H, Mo X, Yang Y, He K, Xiao J, Liu C, Chen J, Lin Y. Association between aflatoxin B1 occupational airway exposure and risk of hepatocellular carcinoma: a case-control study. Tumour Biol 2014; 35:9577-9584. [PMID: 24961349 PMCID: PMC4213372 DOI: 10.1007/s13277-014-2231-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Accepted: 06/11/2014] [Indexed: 12/13/2022] Open
Abstract
The aim of this study was to determine the airway exposure of sugar and papermaking factory workers to aflatoxin B1 (AFB1) and to explore the potential association between AFB1 airway exposure and the risk of hepatocellular carcinoma (HCC) in a case-control study. Dust samples were collected from the sugarcane bagasse warehouse, and presser and paper production workshops. Blood samples were collected from 181 workshop employees and 203 controls who worked outside the workshop. AFB1 albumin adducts were detected using a double antibody sandwich enzyme-linked immunosorbent assay (ELISA). To explore the association between AFB1 airway exposure and the risk of HCC, the medical records of 68 HCC patients who worked in a sugar and papermaking factory between January 1994 and December 2013 were analyzed. A questionnaire was used to collect information from 150 healthy controls who worked for the same company and lived near the factory. AFB1 was detected in the dust samples, but could not be detected in any of the rice samples. An analysis of serum samples revealed serum AFB1 albumin adducts in 102 (56.35 %) of the study participants. However, in the control group, only 12 (5.9 %) individuals had detectable levels of AFB1 albumin adducts. Those with airway exposure to Aspergillus flavus-contaminated dust had an elevated risk of HCC compared to those without exposure (odds ratio, 5.24; 95 % confidence interval, 2.77-9.88; P = 0.00). The findings of this study indicate that occupational AFB1 airway exposure might be associated with the risk of AFB1-related HCC among the population that was used in this study. Intervention programs aimed at reducing exposure to inhalational AFB1 are needed urgently. Additional suitably designed, multicenter, prospective studies using large samples are needed to further confirm the results.
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Affiliation(s)
- Hao Lai
- Department of Gastrointestinal Surgery, Affiliated Cancer Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021 Guangxi Autonomous Region China
| | - Xianwei Mo
- Department of Gastrointestinal Surgery, Affiliated Cancer Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021 Guangxi Autonomous Region China
| | - Yang Yang
- Department of Gastrointestinal Surgery, Affiliated Cancer Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021 Guangxi Autonomous Region China
| | - Ke He
- Department of Head and Neck Surgery, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, 530021 Guangxi Autonomous Region China
| | - Jun Xiao
- Department of Gastrointestinal Surgery, Affiliated Cancer Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021 Guangxi Autonomous Region China
| | - Chao Liu
- Department of Gastrointestinal Surgery, Affiliated Cancer Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021 Guangxi Autonomous Region China
| | - Jiansi Chen
- Department of Gastrointestinal Surgery, Affiliated Cancer Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021 Guangxi Autonomous Region China
| | - Yuan Lin
- Department of Gastrointestinal Surgery, Affiliated Cancer Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021 Guangxi Autonomous Region China
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Xie Y, Liu S, Zhao Y, Guo Z, Xu J. X protein mutations in hepatitis B virus DNA predict postoperative survival in hepatocellular carcinoma. Tumour Biol 2014; 35:10325-31. [PMID: 25034530 DOI: 10.1007/s13277-014-2331-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2014] [Accepted: 07/08/2014] [Indexed: 12/13/2022] Open
Abstract
Hepatitis B virus (HBV) DNA is prone to mutations because of the proofreading deficiencies of HBV polymerase. The postoperative prognostic value of HBV mutations in HBV X protein (HBx) gene was assessed in HBV associated hepatocellular carcinoma (HCC) patients. The HBx gene was amplified and sequenced, the HBV mutations was identified according to NCBI database ( http://www.ncbi.nlm.nih.gov/genome/5536 ). The relationship between the HBV mutations and HCC survival was compared. Survival curves were generated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. After adjusting for clinical characteristics, the following eight mutational sites were identified as statistically significant independent predictors of HCC survival: 1383, 1461, 1485, 1544, 1613, 1653, 1719, and 1753. In addition, the following four mutational sites were identified for their association with survival at a border-line significance level: 1527, 1637, 1674, and 1762/1764. A total of 12 mutations in HBx gene region were identified as independent predictors of postoperative survival in HCC patients. The analysis of HBV DNA mutations may help identify patient subgroups with poor prognosis and may help refine therapeutic decisions regarding HCC patients.
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Affiliation(s)
- Ying Xie
- Hebei Key Lab of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, People's Republic of China
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27
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Lai H, Mo X, Yang Y, He K, Xiao J, Liu C, Chen J, Lin Y. Association between aflatoxin B1 occupational airway exposure and risk of hepatocellular carcinoma: a case-control study. Tumour Biol 2014. [PMID: 24961349 DOI: 10.1007/-s13277-014-2231-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The aim of this study was to determine the airway exposure of sugar and papermaking factory workers to aflatoxin B1 (AFB1) and to explore the potential association between AFB1 airway exposure and the risk of hepatocellular carcinoma (HCC) in a case-control study. Dust samples were collected from the sugarcane bagasse warehouse, and presser and paper production workshops. Blood samples were collected from 181 workshop employees and 203 controls who worked outside the workshop. AFB1 albumin adducts were detected using a double antibody sandwich enzyme-linked immunosorbent assay (ELISA). To explore the association between AFB1 airway exposure and the risk of HCC, the medical records of 68 HCC patients who worked in a sugar and papermaking factory between January 1994 and December 2013 were analyzed. A questionnaire was used to collect information from 150 healthy controls who worked for the same company and lived near the factory. AFB1 was detected in the dust samples, but could not be detected in any of the rice samples. An analysis of serum samples revealed serum AFB1 albumin adducts in 102 (56.35 %) of the study participants. However, in the control group, only 12 (5.9 %) individuals had detectable levels of AFB1 albumin adducts. Those with airway exposure to Aspergillus flavus-contaminated dust had an elevated risk of HCC compared to those without exposure (odds ratio, 5.24; 95 % confidence interval, 2.77-9.88; P = 0.00). The findings of this study indicate that occupational AFB1 airway exposure might be associated with the risk of AFB1-related HCC among the population that was used in this study. Intervention programs aimed at reducing exposure to inhalational AFB1 are needed urgently. Additional suitably designed, multicenter, prospective studies using large samples are needed to further confirm the results.
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Affiliation(s)
- Hao Lai
- Department of Gastrointestinal Surgery, Affiliated Cancer Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021, Guangxi Autonomous Region, China
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Mohd-Redzwan S, Jamaluddin R, Abd-Mutalib MS, Ahmad Z. A mini review on aflatoxin exposure in Malaysia: past, present and future. Front Microbiol 2013; 4:334. [PMID: 24312084 PMCID: PMC3826065 DOI: 10.3389/fmicb.2013.00334] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Accepted: 10/22/2013] [Indexed: 01/24/2023] Open
Abstract
This mini review article described the exposure of aflatoxin in Malaysia, including its presence in the foodstuffs and the detection of aflatoxin biomarkers in human biological samples. Historically, the exposure of aflatoxin in Malaysia can be dated in 1960s where an outbreak of disease in pig farms caused severe liver damage to the animals. Later, an aflatoxicosis case in Perak in 1988 was reported and caused death to 13 children, as up to 3 mg of aflatoxin was present in a single serving of contaminated noodles. Since then, extensive research on aflatoxin has been conducted in Malaysia. The food commodities such as peanuts, cereals, spices, and their products are the main commodities commonly found to be contaminated with aflatoxin. Surprisingly, some of the contaminated foods had levels greater than the permissible limit adopted by the Malaysian Food Regulation 1985. Besides, exposure assessment through the measurement of aflatoxin biomarkers in human biological samples is still in its infancy stage. Nevertheless, some studies had reported the presence of these biomarkers. In fact, it is postulated that Malaysians are moderately exposed to aflatoxin compared to those high risk populations, where aflatoxin contamination in the diets is prevalent. Since the ingestion of aflatoxin could be the integral to the development of liver cancer, the incidence of cancer attributable by dietary aflatoxin exposure in Malaysia has also been reported and published in the literatures. Regardless of these findings, the more important task is to monitor and control humans from being exposed to aflatoxin. The enforcement of law is insufficient to minimize human exposure to aflatoxin. Preventive strategies include agricultural, dietary, and clinical measures should be implemented. With the current research on aflatoxin in Malaysia, a global networking for research collaboration is needed to expand the knowledge and disseminate the information to the global scientific community.
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Affiliation(s)
- Sabran Mohd-Redzwan
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
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29
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Cristina Sass D, Vincenzi Jager A, Gustavo Tonin F, Naira Zambelli Ramalho L, Silva Ramalho F, Gomes Constantino M, Augusto Fernandes Oliveira C. Methods for chemical preparation of aflatoxin B1adducts, AFB1-N7-guanine and AFB1-lysine. TOXIN REV 2013. [DOI: 10.3109/15569543.2013.852110] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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30
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Ren W, Qi X, Yang Z, Han G, Fan D. Prevalence and risk factors of hepatocellular carcinoma in Budd-Chiari syndrome: a systematic review. Eur J Gastroenterol Hepatol 2013; 25:830-841. [PMID: 23411869 DOI: 10.1097/meg.0b013e32835eb8d4] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Budd-Chiari syndrome (BCS) can be incidentally complicated by hepatocellular carcinoma (HCC), thereby decreasing the survival of these patients. Our study aims to systematically review the prevalence and risk factors of HCC in BCS patients. METHODS A PubMed search was performed to identify all original articles that reported the prevalence and risk factors of HCC in BCS patients. Primary items were the prevalence and risk factors of HCC in BCS patients. RESULTS Of 1487 articles identified, 16 were included in our study. The prevalence of HCC in BCS is 2.0-46.2% in 12 Asian studies, 40.0-51.6% in two African studies, 11.3% in one European study, and 11.1% in one American study. Irrespective of hepatitis as the underlying risk factor of HCC, the pooled prevalence of HCC was 17.6% in BCS patients [95% confidence interval (CI): 10.1-26.7%], 26.5% in inferior vena cava obstruction (95% CI: 14.4-40.7%), and 4.2% in hepatic vein obstruction (95% CI: 1.6-7.8%). As patients with HCC and concomitant hepatitis were excluded, the pooled prevalence of HCC was 15.4% in BCS patients (95% CI: 6.8-26.7%). Heterogeneity among studies was statistically significant in these meta-analyses. The risk factors of HCC in BCS included hepatic venous pressure gradient and female sex in two Asian studies, and male sex, factor V Leiden mutation, and inferior vena cava obstruction in one European study. CONCLUSION HCC was frequent in BCS. However, there was a huge variation among studies. Routine surveillance for HCC is warranted in BCS patients. The risk factors of HCC in BCS may vary depending on the geographic origin of the studies.
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Affiliation(s)
- Weirong Ren
- Department of Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
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31
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Li GB, Zhang XL, Yuan L, Jiao QQ, Liu DJ, Liu J. Protein phosphatase magnesium-dependent 1δ (PPM1D) mRNA expression is a prognosis marker for hepatocellular carcinoma. PLoS One 2013; 8:e60775. [PMID: 23556002 PMCID: PMC3610683 DOI: 10.1371/journal.pone.0060775] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2012] [Accepted: 03/02/2013] [Indexed: 12/28/2022] Open
Abstract
Background Protein phosphatase magnesium-dependent 1δ (PPM1D) is an oncogene, overexpressed in many solid tumors, including ovarian cancer and breast cancer. The current study examined the expression and the prognostic value of PPM1D mRNA in human hepatocellular carcinoma (HCC). Methods Total RNA was extracted from 86 HCC and paired non-cancerous liver tissues. PPM1D mRNA expression was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qPCR). Immunohistochemistry assay was used to verify the expression of ppm1d protein in the HCC and non-cancerous liver tissues. HCC patients were grouped according to PPM1D mRNA expression with the average PPM1D mRNA level in non-cancerous liver tissue samples as the cut-off. Correlations between clinicopathologic variables, overall survival and PPM1D mRNA expression were analyzed. Findings PPM1D mRNA was significantly higher in HCC than in the paired non-cancerous tissue (p<0.01). This was confirmed by ppm1d staining. 56 patients were classified as high expression group and the other 30 patients were categorized as low expression group. There were significant differences between the two groups in term of alpha-fetoprotein (α-FP) level (p<0.01), tumor size (p<0.01), TNM stage (p<0.01), recurrence incidence (p<0.01) and family history of liver cancer (p<0.01). The current study failed to find significant differences between the two groups in the following clinical characteristics: age, gender, portal vein invasion, lymphnode metastasis, hepatitis B virus (HBV) infection and alcohol intake. Survival time of high expression group was significantly shorter than that of low expression group (median survival, 13 months and 32 months, respectively, p<0.01). Conclusion Up-regulation of PPM1D mRNA was associated with progressive pathological feature and poor prognosis in HCC patients. PPM1D mRNA may serve as a prognostic marker in HCC.
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Affiliation(s)
- Guang-Bing Li
- Department of Liver Transplantation and Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People's Republic of China
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Liang T, Chen EQ, Tang H. Hepatitis B virus gene mutations and hepatocarcinogenesis. Asian Pac J Cancer Prev 2013; 14:4509-4513. [PMID: 24083693 DOI: 10.7314/apjcp.2013.14.8.4509] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Chronic hepatitis B virus (HBV) infection has long been the most common cause of hepatocellular carcinoma (HCC). However, some aspects of the pathogenesis of HBV infection and genesis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) are still inconclusive. An increasing number of published studies indicate that hepatitis B virus mutations are associated with risk of HCC. These variations include, in particular, mutations in ORF S,C,X gene regions. This mini-review summarizes results of clinical studies and molecular mechanisms on the possible relations of HBV mutations with the development of hepatocellular carcinoma.
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Affiliation(s)
- Tao Liang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China E-mail :
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33
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Wu HC, Santella R. The role of aflatoxins in hepatocellular carcinoma. HEPATITIS MONTHLY 2012; 12:e7238. [PMID: 23162603 PMCID: PMC3496858 DOI: 10.5812/hepatmon.7238] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/21/2012] [Revised: 06/29/2012] [Accepted: 07/11/2012] [Indexed: 12/11/2022]
Abstract
CONTEXT Hepatocellular carcinoma (HCC) is one of the most common cancers in the world but with a striking geographical variation in incidence; most of the burden is in developing countries. This geographic variation in HCC incidence might be due to geographic differences in the prevalence of various etiological factors. EVIDENCE ACQUISITION Here, we review the epidemiological evidence linking dietary exposure to aflatoxin B1 (AFB1) and risk of HCC, possible interactions between AFB1 and hepatitis B virus (HBV) or polymorphisms of genes involved in AFB1-related metabolism as well as DNA repair. RESULTS Ecological, case-control and cohort studies that used various measures of aflatoxin exposure including dietary questionnaires, food surveys and biomarkers are summarized. CONCLUSIONS Taken together, the data suggest that dietary exposure to aflatoxins is an important contributor to the high incidence of HCC in Asia and sub-Saharan Africa, where almost 82% of the cases occur.
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Affiliation(s)
- Hui Chen Wu
- Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, USA
| | - Regina Santella
- Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, USA
- Corresponding author: Regina Santella, Department of Environmental Health Sciences Mailman School of Public Health of Columbia University 630 West 168th St, New York, NY 10032, USA. Tel.: +21-23051996, Fax: +21-23055328, E-mail:
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Evaluation of hazard of aflatoxin B1, ochratoxin A and patulin production in dry-cured ham and early detection of producing moulds by qPCR. Food Control 2012. [DOI: 10.1016/j.foodcont.2012.03.009] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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35
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Exposure measurement of aflatoxins and aflatoxin metabolites in human body fluids. A short review. Mycotoxin Res 2012; 28:79-87. [DOI: 10.1007/s12550-012-0129-8] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Revised: 03/06/2012] [Accepted: 03/07/2012] [Indexed: 01/09/2023]
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36
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Leong YH, Rosma A, Latiff AA, Izzah AN. Associations of serum aflatoxin B1-lysine adduct level with socio-demographic factors and aflatoxins intake from nuts and related nut products in Malaysia. Int J Hyg Environ Health 2012; 215:368-72. [PMID: 22230243 DOI: 10.1016/j.ijheh.2011.12.005] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2011] [Revised: 12/05/2011] [Accepted: 12/08/2011] [Indexed: 11/15/2022]
Abstract
Aflatoxins are one of the major risk factors in the multi-factorial etiology of human hepatocellular carcinoma. Therefore, the information on aflatoxins exposure is very important in the intervention planning in order to reduce the dietary intake of aflatoxins, especially among the children. This study investigated the relationship between aflatoxin B(1) (AFB(1)) lysine adduct levers in serum and socio-demographic factors and dietary intake of aflatoxins from nuts and nut products in Penang, Malaysia. A cross-sectional field study was conducted in five districts of Penang. A survey on socio-demographic characteristics was administered to 364 healthy adults from the three main ethnic groups (Malay, Chinese and Indian). A total of 170 blood samples were successfully collected and tested for the level of AFB(1)-lysine adduct. 97% of the samples contained AFB(1)-lysine adduct above the detection limit of 0.4 pg/mg albumin and ranged from 0.20 to 23.16 pg/mg albumin (mean±standard deviation=7.67±4.54 pg/mg albumin; median=7.12 pg/mg albumin). There was no significant association between AFB(1)-lysine adduct levels with gender, district, education level, household number and occupation when these socio-demographic characteristics were examined according to high or low levels of AFB(1)-lysine. However, participants in the age group of 31-50 years were 3.08 times more likely to have high AFB(1) levels compared to those aged between 18 and 30 years (P=0.026). Significant difference (P=0.000) was found among different ethnic groups. Chinese and Indian participants were 3.05 and 2.35 times more likely to have high AFB(1) levels than Malay. The result of AFB(1)-lysine adduct suggested that Penang adult population is likely to be exposed to AFB(1) but at a level of less than that needed to cause direct acute illness or death.
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Affiliation(s)
- Yin-Hui Leong
- Doping Control Centre, Universiti Sains Malaysia, 11800 Penang, Malaysia
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Tan YJ. Hepatitis B virus infection and the risk of hepatocellular carcinoma. World J Gastroenterol 2011; 17:4853-7. [PMID: 22171125 PMCID: PMC3235627 DOI: 10.3748/wjg.v17.i44.4853] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2011] [Revised: 07/06/2011] [Accepted: 07/13/2011] [Indexed: 02/06/2023] Open
Abstract
Epidemiological studies have provided overwhelming evidence for a causal role of chronic hepatitis B virus (HBV) infection in the development of hepatocellular carcinoma (HCC). However, the pathogenesis of HBV infection and carcinogenesis of HBV-associated HCC are still elusive. This review will summarize the current knowledge on the mechanisms involved in HBV-related liver carcinogenesis. The role of HBV in tumor formation appears to be complex, and may involve both direct and indirect mechanisms. Integration of HBV DNA into the host genome occurs at early steps of clonal tumor expansion, and it has been shown to enhance the host chromosomal instability, leading to large inverted duplications, deletions and chromosomal translocations. It has been shown that the rate of chromosomal alterations is increased significantly in HBV-related tumors. Prolonged expression of the viral regulatory HBV x protein may contribute to regulating cellular transcription, protein degradation, proliferation, and apoptotic signaling pathways, and it plays a critical role in the development of hepatocellular carcinoma.
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