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Zhang Y, Cao W, Wang S, Zhang L, Li X, Zhang Z, Xie Y, Li M. Epigenetic modification of hepatitis B virus infection and related hepatocellular carcinoma. Virulence 2024; 15:2421231. [PMID: 39460469 PMCID: PMC11583590 DOI: 10.1080/21505594.2024.2421231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 09/18/2024] [Accepted: 10/21/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatitis B virus (HBV) infection poses a challenge to global public health. Persistent liver infection with HBV is associated with an increased risk of developing severe liver disease. The complex interaction between the virus and the host is the reason for the persistent presence of HBV and the risk of tumor development. Chronic liver inflammation, integration of viral genome with host genome, expression of HBx protein, and viral genotype are all key participants in the pathogenesis of hepatocellular carcinoma (HCC). Epigenetic regulation in HBV-associated HCC involves complex interactions of molecular mechanisms that control gene expression and function without altering the underlying DNA sequence. These epigenetic modifications can significantly affect the onset and progression of HCC. This review summarizes recent research on the epigenetic regulation of HBV persistent infection and HBV-HCC development, including DNA methylation, histone modification, RNA modification, non-coding RNA, etc. Enhanced knowledge of these mechanisms will offer fresh perspectives and potential targets for intervention tactics in HBV-HCC.
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Affiliation(s)
- Yaqin Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Weihua Cao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shiyu Wang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xinxin Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ziyu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
| | - Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China
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Liu L, Chen J, Ye F, Chu F, Rao C, Wang Y, Yan Y, Wu J. Prognostic value of oxidative phosphorylation-related genes in hepatocellular carcinoma. Discov Oncol 2024; 15:258. [PMID: 38960931 PMCID: PMC11222354 DOI: 10.1007/s12672-024-01129-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 06/27/2024] [Indexed: 07/05/2024] Open
Abstract
PURPOSE Hepatocellular carcinoma (HCC) is the most prevalent malignancies worldwide. Recently, oxidative phosphorylation (OXPHOS) has received extensive concern as an emerging target in antitumor therapy. However, the OXPHOS-involved underlying genes and clinical utilization in HCC remain worth exploring. The present research aimed to create an OXPHOS-relevant signature in HCC. PATIENTS AND METHODS In this study, the prognostic signature genes linked with OXPHOS were identified, and prognostic models were built using least absolute shrinkage and selection operator (LASSO) cox regression analysis. Furthermore, the combination study of immune microenvironment and signature genes looked into the involvement of immune cells in signature-based genes in HCC. Following that, chemotherapeutic drug sensitivity and immunotherapy analysis was implemented to predict clinical efficacy in HCC patients. Finally, clinical samples were collected to measure the expression of OXPHOS-related signature genes. RESULTS Following a series of screens, six prognostic signature genes related with OXPHOS were identified: MRPS23, MPV17, MAPK3, IGF2BP2, CDK5, and IDH2, on which a risk model was built. The findings revealed a significant drop in the survival rate of HCC patients as their risk score increased. Meanwhile, independent prognostic study demonstrated that the risk score could accurately identify HCC patients. Immuno-microenvironmental correlation research suggested that the prognostic characteristics could serve as a reference index for both immunotherapy and chemotherapy. Finally, RT-qPCR exhibited a trend in signature gene expression that was consistent with the results. CONCLUSION In this study, a total of six prognostic genes associated with OXPHOS were selected and a prognostic model was constructed, providing an essential reference for the study of OXPHOS in HCC.
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Affiliation(s)
- Luzheng Liu
- Department of Interventional Radiology and Vascular Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570100, Hainan Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, China
| | - Jiacheng Chen
- Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, China
| | - Fei Ye
- Department of Blood Cell Therapy, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570100, Hainan Province, China
| | - Fengran Chu
- Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, China
| | - Chaoluan Rao
- Department of Nursing, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570100, Hainan Province, China
| | - Yong Wang
- Department of Interventional Radiology and Vascular Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570100, Hainan Province, China
| | - Yanggang Yan
- Department of Interventional Radiology and Vascular Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, 570100, Hainan Province, China.
| | - Jincai Wu
- Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan Province, China.
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Varghese N, Majeed A, Nyalakonda S, Boortalary T, Halegoua-DeMarzio D, Hann HW. Review of Related Factors for Persistent Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:777. [PMID: 38398168 PMCID: PMC10887172 DOI: 10.3390/cancers16040777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 01/30/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV's covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies. Some studies suggest that HBV undergoes compartmentalization in peripheral blood mononuclear cells that serve as a sanctuary for replication during antiviral therapy. The aim of this review is to expand on how patients with HBV may develop HCC despite years of HBV viral suppression and carry worse prognosis than treatment-naive HBV patients who develop HCC. Furthermore, HCC recurrence after initial surgical or locoregional treatment in this setting may cause carcinogenic cells to behave more aggressively during treatment. Curative novel therapies which target the life cycle of HBV, modulate host immune response, and inhibit HBV RNA translation are being investigated.
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Affiliation(s)
- Nevin Varghese
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
| | - Amry Majeed
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
| | - Suraj Nyalakonda
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
| | - Tina Boortalary
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Hie-Won Hann
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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Fernandes Q, Inchakalody VP, Bedhiafi T, Mestiri S, Taib N, Uddin S, Merhi M, Dermime S. Chronic inflammation and cancer; the two sides of a coin. Life Sci 2024; 338:122390. [PMID: 38160787 DOI: 10.1016/j.lfs.2023.122390] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 12/21/2023] [Accepted: 12/24/2023] [Indexed: 01/03/2024]
Abstract
The correlation between chronic inflammation and cancer was initially identified in the 19th century. Biomolecules like interleukins, chemokines, tumor necrosis factors, growth factors, and adhesion molecules, which regulate inflammation, are recognized contributors to neoplastic transformation through various mechanisms, including oncogenic mutations, resistance to apoptosis, and adaptive responses like angiogenesis. This review aims to establish connections between the intricate and complex mechanisms of chronic inflammation and cancer. We illuminate implicit signaling mechanisms that drive the association between chronic inflammation and the initiation/progression of cancer, exploring potential impacts on other diseases. Additionally, we discuss the modalities of currently available therapeutic options for chronic inflammation and cancer, emphasizing the dual nature of such therapies. A thorough understanding of the molecular basis of chronic inflammation is crucial for developing novel approaches in the prevention and treatment of cancer.
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Affiliation(s)
- Queenie Fernandes
- Translational Cancer Research Facility, National Center for Cancer Care and Research, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar; College of Medicine, Qatar University, Doha, Qatar
| | - Varghese Philipose Inchakalody
- Translational Cancer Research Facility, National Center for Cancer Care and Research, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Takwa Bedhiafi
- Translational Cancer Research Facility, National Center for Cancer Care and Research, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Sarra Mestiri
- Translational Cancer Research Facility, National Center for Cancer Care and Research, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Nassiba Taib
- Translational Cancer Research Facility, National Center for Cancer Care and Research, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Shahab Uddin
- Translational Research Institute and Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar; Laboratory Animal Research Center, Qatar University, Doha, Qatar
| | - Maysaloun Merhi
- Translational Cancer Research Facility, National Center for Cancer Care and Research, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar.
| | - Said Dermime
- Translational Cancer Research Facility, National Center for Cancer Care and Research, Translational Research Institute, Hamad Medical Corporation, Doha, Qatar; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
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Osasona OG, Oguntoye OO, Arowosaye AO, Abdulkareem LO, Adewumi MO, Happi C, Folarin O. Patterns of hepatitis b virus immune escape and pol/rt mutations across clinical cohorts of patients with genotypes a, e and occult hepatitis b infection in Nigeria: A multi-centre study. Virulence 2023; 14:2218076. [PMID: 37262110 DOI: 10.1080/21505594.2023.2218076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 03/27/2023] [Accepted: 05/20/2023] [Indexed: 06/03/2023] Open
Abstract
Hepatitis B virus (HBV) immune escape and Pol/RT mutations account for HBV immunoprophylactic, therapeutic, and diagnostic failure globally. Little is known about circulating HBV immune escape and Pol/RT mutants in Nigeria. This study focused on narrowing the knowledge gap of the pattern and prevalence of the HBV mutants across clinical cohorts of infected patients in southwestern Nigeria. Ninety-five enrollees were purposively recruited across clinical cohorts of HBV-infected patients with HBsAg or anti-HBc positive serological outcome and occult HBV infection. Total DNA was extracted from patients' sera. HBV S and Pol gene-specific nested PCR amplification was carried out. The amplicons were further sequenced for serotypic, genotypic, phylogenetic, and mutational analysis. HBV S and Pol genes were amplified in 60 (63.2%) and 19 (20%) of HBV isolates, respectively. All the sixty HBV S gene and 14 of 19 Pol gene sequences were exploitable. The ayw4 serotype was predominant (95%) while ayw1 serotype was identified in 5% of isolates. Genotype E predominates in 95% of sequences, while genotype A, sub-genotype A3 was observed in 5%. Prevalence of HBV IEMs in the "a" determinant region was 29%. Commonest HBV IEM was S113T followed by G145A and D144E. The Pol/RT mutations rtV214A and rtI163V among others were identified in this study. This study provided data on the occurrence of existing and new HBV IEMs and Pol gene mutations in Nigeria.
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Affiliation(s)
- Oluwadamilola G Osasona
- African Centre of Excellence for the Genomics of Infectious Diseases, Redeemers University, Ede, Nigeria
| | | | - Abiola O Arowosaye
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Lukman O Abdulkareem
- Department of Internal Medicine, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria
| | - Moses O Adewumi
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Christian Happi
- African Centre of Excellence for the Genomics of Infectious Diseases, Redeemers University, Ede, Nigeria
| | - Onikepe Folarin
- African Centre of Excellence for the Genomics of Infectious Diseases, Redeemers University, Ede, Nigeria
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Badshah Y, Shabbir M, Zafar S, Mussarat U, Ikram A, Javed S, Akhtar H. Impact of IL-12B Genetic Variants on Antiviral Treatment Response among Hepatitis B Patients in Pakistan. LIVERS 2023; 3:494-506. [DOI: 10.3390/livers3030034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2025] Open
Abstract
HBV is a continuous major global health concern. Genetic factors of hosts are known to play a role in HBV infection outcomes. This study aimed to reveal the association of IL-12b 3′ UTR variant rs3212227 in HBV patients. Genotyping was performed using ARMS-PCR to detect IL-12b rs3212227 polymorphism. The patients were categorized into groups based on their response to the antiviral therapy. Group I: non-sustained virological response (NSR); Group II: sustained virological responders (SVR); and Group III: HBV-positive fresh cases. ALT levels were measured to evaluate liver function, and viral load was determined to evaluate viral infectivity among the study groups. The variant genotype CC was found to be significantly associated with the non-sustained virological response to the antiviral therapy (with a p-value of 0.0117; OR = 2.914; RR = 1.556). It was also determined that the genotype CC was the most prevalent genotype among both genders in the NSR group. Viral load was found to be 6-fold higher in Group III compared to Group I and Group II. The results suggest that genotype CC is the most prevalent genotype in the NSR groups, and it is associated with a poor response to antiviral therapy in Pakistani patients with HBV infection.
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Affiliation(s)
- Yasmin Badshah
- Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan
| | - Maria Shabbir
- Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan
| | - Sameen Zafar
- Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 44000, Pakistan
| | - Uzma Mussarat
- Department of Pathology (Microbiology), Islamic International Medical College, Rawalpindi 46000, Pakistan
| | - Aamer Ikram
- Global Health Security Agenda (GHSA), Center for Disease Control (CDC), National Institute of Health (NIH), Islamabad 44000, Pakistan
| | - Sumbal Javed
- Global Health Security Agenda (GHSA), Center for Disease Control (CDC), National Institute of Health (NIH), Islamabad 44000, Pakistan
| | - Hashaam Akhtar
- Global Health Security Agenda (GHSA), Center for Disease Control (CDC), National Institute of Health (NIH), Islamabad 44000, Pakistan
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7
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Wang W, Jia H, Wang Y, Sun W, Yang C. Predictive Value of Inflammatory Cytokines in Early Pregnancy for Liver Dysfunction in Pregnant Women with Hepatitis B. Horm Metab Res 2023; 55:59-64. [PMID: 36446568 DOI: 10.1055/a-1973-7255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
The purpose of this study is to explore the predictive value of cytokine levels in the first trimester of pregnancy on abnormal liver function of pregnant women with hepatitis B in the third trimester of pregnancy. A total of 111 pregnant women with HBV infection at 12 weeks gestation participated in the study. The levels of IL-6, IL-8, TNF-α in peripheral blood of the patients and liver function indexes were detected. Subsequently, the pregnant women were followed up, and the liver function was detected at 36 weeks of gestation. According to liver function indexes, patients were divided into normal liver function group and abnormal liver function group to determine the correlation between cytokines in early pregnancy and abnormal liver function in late pregnancy. Kaplan-Meier survival curve and multivariate Cox analysis were used to evaluate the predictive value of cytokines for liver dysfunction. At 12 weeks of gestation, cytokine levels in the normal liver function group were significantly lower than that in the abnormal liver function group. Kaplan-Meier survival analysis showed that the increased IL-6 level was associated with abnormal liver function in late pregnancy. Multivariate Cox regression analysis revealed that IL-6 level was an independent predictor of abnormal liver function in patients with normal liver function in the late pregnancy. The high expression level of cytokine IL-6 at 12 weeks of pregnancy has noteworthy predictive significance for the abnormal liver function of hepatitis B pregnant women in third trimester of pregnancy.
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Affiliation(s)
- Wei Wang
- Department of Science and Education, Shijiazhuang Maternity and Child Healthcare Hospital, Shijiazhuang, China
| | - Hongyan Jia
- Department of Infection Control Division, Shijiazhuang Maternity and Child Healthcare Hospital, Shijiazhuang, China
| | - Yue Wang
- Department of Internal Medicine, Shijiazhuang Third Hospital, Shijiazhuang, China
| | - Weize Sun
- Department of Obstetrics and Gynecology, Ningjin County Maternity and Child Healthcare Hospital, Xingtai, China
| | - Can Yang
- Department of Internal Medicine, Shijiazhuang Maternity and Child Healthcare Hospital, Shijiazhuang, China
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Overexpressed RING Finger 44 Correlates with Poor Prognosis in Hepatocellular Carcinoma. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:3522866. [PMID: 35494516 PMCID: PMC9042607 DOI: 10.1155/2022/3522866] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 03/18/2022] [Accepted: 03/21/2022] [Indexed: 12/24/2022]
Abstract
Introduction Liver carcinoma is one of the most common cancers in the world and remains one of the most difficult cancers to treat. Hepatocellular cancer is the most important type of liver cancer (90%). RING Finger 44 (RNF44) is one of the E3 ligases, which play an important role in substrate recognition. It was also reported that RING Finger 44 was connected with resistant melanoma. But the relationship between RNF44 and HCC remained unknown. Materials and Methods To analyze the role of RING Finger 44 gene in hepatocellular carcinoma, we used bioinformatics to analyze the expression level, genetic changes, immunohistochemistry, immune infiltration, diagnostic value, survival, and functional enrichment of RING Finger 44. Results Through analyzing The Genotype-Tissue Expression and The Cancer Genome Atlas databases, we found that the expression level of RING Finger 44 was significantly increased in hepatocellular carcinoma tissues. Meanwhile, the expression of RING Finger 44 was connected with immune cell infiltration and survival time, and the expression level of RING Finger 44 could perform as a useful diagnostic and prognostic index. The functional enrichment analysis of RING Finger 44 provided some possible pathways of RING Finger 44 in hepatocellular carcinoma, which provided an important direction for the further experiments in vitro or in vivo. Conclusions RING Finger 44, the high expression level of which predicts poor prognosis, is a potential oncogene in hepatocellular carcinoma.
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Noverati N, Bashir-Hamidu R, Halegoua-DeMarzio D, Hann HW. Hepatitis B Virus-Associated Hepatocellular Carcinoma and Chronic Stress. Int J Mol Sci 2022; 23:3917. [PMID: 35409275 PMCID: PMC8999024 DOI: 10.3390/ijms23073917] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 03/29/2022] [Accepted: 03/30/2022] [Indexed: 01/27/2023] Open
Abstract
The Hepatitis B virus is one of the most significant hepatocarcinogens globally. The carcinogenic mechanisms of this virus are complex, and may include interactions with the host's immune system. Certain factors, such as stress on the body, can also potentiate these mechanisms. Stress, although adaptive in an acute form, is deleterious to health when chronic and can both suppress and activate the host's defense system. In hepatocellular carcinoma, this can lead to tumor initiation and progression. Those that are more prone to stress, or exposed to situations that incite stress, may be at higher risk of developing cancer. Racial disparities, for example, are a source of chronic psychosocial stress in America and predispose minorities to poorer outcomes. As it remains perplexing why some individuals with chronic hepatitis B develop feared complications while others do not, it is important to recognize as many risk factors as possible, including those often overlooked such as chronic stress.
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Affiliation(s)
- Nicholas Noverati
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.N.); (R.B.-H.); (D.H.-D.)
| | - Rukaiya Bashir-Hamidu
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.N.); (R.B.-H.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.N.); (R.B.-H.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Hie-Won Hann
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.N.); (R.B.-H.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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10
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CHEN TT, DU SL, WANG SJ, WU L, YIN L. Dahuang Zhechong pills inhibit liver cancer growth in a mouse model by reversing Treg/Th1 balance. Chin J Nat Med 2022; 20:102-110. [DOI: 10.1016/s1875-5364(22)60160-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Indexed: 11/03/2022]
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Chen Y, Wei D, Deng M. Comparative Analysis of Serum Proteins Between Hepatitis B Virus Genotypes B and C Infection by DIA-Based Quantitative Proteomics. Infect Drug Resist 2021; 14:4701-4715. [PMID: 34795487 PMCID: PMC8592397 DOI: 10.2147/idr.s335666] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 10/28/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose In clinical practice, the clinicopathological profiles and outcomes of patients infected with hepatitis B virus (HBV) are different between genotypes B and C. However, little is known about the potential mechanism and differences in specific biological pathways associated with the different genotype. This study aimed to compare the serum protein profile between patients infected with HBV genotype B and those infected with HBV genotype C. Patients and Methods A total of 54 serum samples from patients with chronic HBV genotype B infection and those with chronic HBV genotype C infection, and healthy controls were used for the proteomic analysis (n = 18 samples in per group). Serum proteomic profiles were analyzed using data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins (up- or downregulation of at least 1.5-fold) between serum samples from HBV patients infected with HBV genotype B and those infected with genotype C. Results We identified 1010 proteins, 53 of which were differentially expressed between the serum samples of the healthy controls and those of HBV genotype B infected patients, and 59 that were differentially expressed between the samples of the healthy controls and those of HBV genotype C infected patients. Furthermore, our results indicated that two proteins identified as being differentially expressed (VWF and C8B) have potential as biomarkers for distinguishing genotype B infected HBV patients from those infected with genotype C. Conclusion The results of our DIA-based quantitative proteomic analysis revealed that HBV genotypes B and C are associated with different molecular profiles and may provide fundamental information for further detailed investigations of the molecular mechanism underlying these differences.
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Affiliation(s)
- Yunqing Chen
- Department of Infectious Diseases, Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China.,Department of Infectious Diseases, First Hospital of Jiaxing, Jiaxing, People's Republic of China
| | - Dahai Wei
- Department of Infectious Diseases, Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China.,Department of Infectious Diseases, First Hospital of Jiaxing, Jiaxing, People's Republic of China.,Institute of Hepatology, Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China
| | - Min Deng
- Department of Infectious Diseases, Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China.,Department of Infectious Diseases, First Hospital of Jiaxing, Jiaxing, People's Republic of China.,Institute of Hepatology, Affiliated Hospital of Jiaxing University, Jiaxing, People's Republic of China
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12
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Han JJ, Chen Y, Nan YC, Yang YL. Extremely high titer of hepatitis B surface antigen antibodies in a primary hepatocellular carcinoma patient: A case report. World J Clin Cases 2021; 9:8492-8497. [PMID: 34754858 PMCID: PMC8554442 DOI: 10.12998/wjcc.v9.i28.8492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 06/10/2021] [Accepted: 08/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) may be caused by hepatitis B virus (HBV) infection. Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen (HBsAg) level and increased anti-HBsAg antibody titer. Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC development. Here, we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection.
CASE SUMMARY A 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level (over 2000 ng/mL) of serum alpha-fetoprotein. Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly. Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen (anti-HBcAg antibodies), an extremely high titer (1000 mIU/mL) of hepatitis B surface antibodies (anti-HBsAg antibodies, anti-HBs) and absence of detectible HBsAg. Medical records indicated that the patient had reported no history of HBV vaccination, infection or hepatitis. Therefore, to rule out latent HBV infection in this patient, a serum sample was collected then tested to detect HBV DNA, yielding a positive result. Based on the aforementioned information, the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment.
CONCLUSION A rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.
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Affiliation(s)
- Jing-Jing Han
- Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Yu Chen
- Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Yu-Chen Nan
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi Province, China
| | - Yong-Lin Yang
- Department of Infectious Disease, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People's Hospital), Taizhou 225300, Jiangsu Province, China
- Department of General Practice, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
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13
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Effects of transcutaneous electrical acupoint stimulation on perioperative immune function and postoperative analgesia in patients undergoing radical mastectomy: A randomized controlled trial. Exp Ther Med 2021; 21:184. [PMID: 33488793 PMCID: PMC7812592 DOI: 10.3892/etm.2021.9615] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 11/26/2020] [Indexed: 12/23/2022] Open
Abstract
Radical mastectomy may lead to suppression of cellular immune function in patients with malignant tumors. Transcutaneous electrical acupoint stimulation (TEAS) is widely used in clinical practice. However, there have been relatively few studies on the effects of TEAS on postoperative analgesia and immune function. The present study aimed to evaluate the effects of TAES on postoperative pain and immune function in patients undergoing radical mastectomy. A total of 65 patients were enrolled and allocated to either receive TEAS or sham TEAS. TEAS was implemented on bilateral Hegu (LI4), Neiguan (PC6) and Zusanli (ST36) acupoints simultaneously for 30 min before induction of anesthesia at 4 and 12 h post-operation. The primary outcomes included visual analogue scale (VAS) scores at 4 h (T1), 12 h T2), 24 h (T3) and 48 h (T4) post-operation, and serum levels of IL-2, IL-4, IFN-γ and the IL-2/IL-4 ratio at 30 min before TEAS (T0), T1, T2, T3 and T4. Secondary outcomes included the cumulative time of rescue analgesia within 48 h post-surgery, as well as the incidence of postoperative nausea and vomiting (PONV) and pruritus. Compared with the sham TEAS group, postoperative VAS scores at T2 and T3, the total consumption of opioids in the patient-controlled analgesia (PCA) pump, pressing times of the PCA pump and the incidences of PONV and headache were significantly lower in the TEAS group. The serum levels of IFN-γ at T3 and T4, and the serum levels of IL-2 and the IL-2/IL-4 ratio at T2, T3 and T4 were higher in the TEAS group compared with the sham TEAS group. By contrast, the serum levels of IL-4 were lower at T2, T3 and T4 in the TEAS group compared with the sham TEAS group. The results indicated that TEAS could improve postoperative analgesia, reduce postoperative consumption of opioids and alleviate postoperative side effects. Simultaneously, TEAS was able to reverse decreased serum levels of IL-2 and IFN-γ, reduce the level of IL-4 and restore the balance of Th1/Th2, thereby partially attenuating perioperative immune function depression in patients with breast cancer. The current trial was registered prior to participant enrollment at www.chictr.org.cn (Clinical Trial no. ChiCTR1800017768).
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14
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Fu Y, Zhang Y, Khoo BL. Liquid biopsy technologies for hematological diseases. Med Res Rev 2020; 41:246-274. [PMID: 32929726 DOI: 10.1002/med.21731] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 08/10/2020] [Accepted: 09/02/2020] [Indexed: 12/18/2022]
Abstract
Since the discovery of circulating tumor cells in 1869, technological advances in studying circulating biomarkers from patients' blood have made the diagnosis of nonhematologic cancers less invasive. Technological advances in the detection and analysis of biomarkers provide new opportunities for the characterization of other disease types. When compared with traditional biopsies, liquid biopsy markers, such as exfoliated bladder cancer cells, circulating cell-free DNA (cfDNA), and extracellular vesicles (EV), are considered more convenient than conventional biopsies. Liquid biopsy markers undoubtedly have the potential to influence disease management and treatment dynamics. Our main focuses of this review will be the cell-based, gene-based, and protein-based key liquid biopsy markers (including EV and cfDNA) in disease detection, and discuss the research progress of these biomarkers used in conjunction with liquid biopsy. First, we highlighted the key technologies that have been broadly adopted used in hematological diseases. Second, we introduced the latest technological developments for the specific detection of cardiovascular disease, leukemia, and coronavirus disease. Finally, we concluded with perspectives on these research areas, focusing on the role of microfluidic technology and artificial intelligence in point-of-care medical applications. We believe that the noninvasive capabilities of these technologies have great potential in the development of diagnostics and can influence treatment options, thereby advancing precision disease management.
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Affiliation(s)
- Yatian Fu
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon Tong, Hong Kong, China
| | - Yiyuan Zhang
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon Tong, Hong Kong, China
| | - Bee Luan Khoo
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon Tong, Hong Kong, China
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15
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Maponga TG, Glashoff RH, Vermeulen H, Robertson B, Burmeister S, Bernon M, Omoshoro-Jones J, Ruff P, Neugut AI, Jacobson JS, Preiser W, Andersson MI. Hepatitis B virus-associated hepatocellular carcinoma in South Africa in the era of HIV. BMC Gastroenterol 2020; 20:226. [PMID: 32660431 PMCID: PMC7359588 DOI: 10.1186/s12876-020-01372-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 07/07/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Patients co-infected with hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are at risk of developing hepatocellular carcinoma (HCC). In sub-Saharan Africa, the overlap between high HIV and HBV prevalence may increase the incidence of HCC. This study investigated the impact of HBV/HIV co-infection on age at presentation and survival of HCC. METHODS Ethical approval was obtained to recruit, following informed written consent, patients diagnosed with HCC at oncology units at four South African hospitals. Between December 2012 and August 2015, patients newly diagnosed with HCC were recruited and provided demographic and clinical data and blood specimens. Patients were tested for HBV, hepatitis C virus (HCV) and HIV. Survival data was available for a subset of patients. RESULTS Of 107 HCC cases, 83 (78%) were male. Median age was 46 years (range 18 to 90 years), 68/106 (64%) were HBsAg-positive, and 22/100 (22%) were HIV infected. Among HBV surface antigen (HBsAg)-positive HCC cases, 18/66 (27%) were HIV-infected compared to 3/34 (9%) among those that were HBsAg-negative (p = 0.04). A greater proportion of HBV/HIV co-infected cases were female than HBV mono-infected (6/18, 33% vs 6/47, 13%; p = 0.005). In addition, HBV/HIV co-infected females presented at a younger mean age (36.8 years) than HBV mono-infected women (50.5 years) (p = 0.09). Median survival was 82 days among the HIV-infected HCC patients compared to 181 days among those without HIV (p = 0.15). CONCLUSIONS HCC is an important complication in the HIV/HBV infected patient. HIV-positive patients presented with HCC at a younger age than HIV-negative patients, this effect appears to be greater in women. These data provide more evidence supporting the call to address. HCC as a cause of morbidity and mortality in the HBV/HIV co-infected patient population. (281 words).
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Affiliation(s)
- Tongai Gibson Maponga
- Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa.
| | - Richard H Glashoff
- Division of Medical Microbiology & Immunology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa.,Tygerberg Business Unit, National Health Laboratory Service, Cape Town, South Africa
| | - Hannali Vermeulen
- Division of Radiation Oncology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa
| | - Barbara Robertson
- Division of Radiation Oncology, University of Cape Town, Cape Town, South Africa
| | - Sean Burmeister
- Department of Surgery, University of Cape Town, Cape Town, South Africa
| | - Marc Bernon
- Department of Surgery, University of Cape Town, Cape Town, South Africa
| | | | - Paul Ruff
- Division of Medical Oncology, University of Witwatersrand, Johannesburg, South Africa
| | - Alfred I Neugut
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA.,Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, USA.,Mailman School of Public Health, Columbia University, New York, USA
| | - Judith S Jacobson
- Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, USA.,Mailman School of Public Health, Columbia University, New York, USA
| | - Wolfgang Preiser
- Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa.,Tygerberg Business Unit, National Health Laboratory Service, Cape Town, South Africa
| | - Monique I Andersson
- Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa.,Department of Microbiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
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16
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Ben Dhifallah I, Ayouni K, Najjar G, Chelbi H, Sadraoui A, Hammami W, Touzi H, Triki H. Interleukin IL-1B gene polymorphism in Tunisian patients with chronic hepatitis B infection: Association with replication levels. Microbiol Immunol 2020; 64:512-519. [PMID: 31944355 DOI: 10.1111/1348-0421.12774] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 12/16/2019] [Accepted: 01/10/2020] [Indexed: 12/20/2022]
Abstract
Approaches based on association studies have proven useful in identifying genetic predictors for many diseases, including susceptibility to chronic hepatitis B. In this study we were interested by the IL-1B genetic variants that have been involved in the immune response and we analyzed their role in the susceptibility to develop chronic hepatitis B in the Tunisian population. IL-1B is a potent proinflammatory cytokine that plays an important role in inflammation of the liver. Polymorphic gene IL-1 (-511, +3954) was analyzed in a total of 476 individuals: 236 patients with chronic hepatitis B from different cities of Tunisia recruited in Pasteur Institute between January 2017 and December 2018 and 240 controls. Genomic DNA was obtained using the standard salting-out method and genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism. For -511C>T polymorphism a significant association was found between patients and controls when comparing the genotypic (P = 0.007; χ2 = 9.74 and odds ratio [OR] = 0.60; confidence interval [CI] = 0.41-0.89) and allelic (P = 0.001; χ2 = 10.60) frequencies. When the viral load was taken into account a highly significant difference was found (P = 9 × 10-4 ; χ2 = 10.89). For +3954C>T polymorphism a significant association was found between patients and controls when comparing genotypic (P = 0.0058; χ2 = 7.60 and OR = 1.67; CI = 1.14-2.46) and allelic (P = 0.0029; χ2 = 8.81) frequencies. T allele can be used as a strong marker for hepatitis B virus disease for both polymorphisms.
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Affiliation(s)
- Imen Ben Dhifallah
- Laboratory of Clinical Virology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Kaouther Ayouni
- Laboratory of Clinical Virology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia.,Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Ghofrane Najjar
- Laboratory of Clinical Virology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Hanene Chelbi
- Medical Parasitology, Biotechnology and Biomolecules, Pasteur Institute of Tunis, Tunis, Tunisia
| | - Amel Sadraoui
- Laboratory of Clinical Virology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Walid Hammami
- Laboratory of Clinical Virology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Henda Touzi
- Laboratory of Clinical Virology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Henda Triki
- Laboratory of Clinical Virology, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis, Tunisia
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17
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Tian L, Li CM, Li YF, Huang TM, Chao NX, Luo GR, Mo FR. Laminarin from Seaweed ( Laminaria japonica) Inhibits Hepatocellular Carcinoma Through Upregulating Senescence Marker Protein-30. Cancer Biother Radiopharm 2020; 35:277-283. [PMID: 32159381 PMCID: PMC7247046 DOI: 10.1089/cbr.2019.3179] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Objective: This study aimed at investigating the specific roles of laminarin from seaweed (Laminaria japonica) in hepatocellular carcinoma (HCC) and its potential mechanisms related to senescence marker protein-30 (SMP-30). Materials and Methods: Human HCC cell lines, including Bel-7404 and HepG2, were incubated with different concentrations of laminarin (0, 5, 15, 25, 35, and 45 mg/mL). The cell viability and apoptosis rates were detected by WST-8 cell proliferation assay and flow cytometry, respectively. Hepa 1–6 tumor-bearing mice were injected with different concentrations of laminarin (400, 800, and 1200 mg/kg·d), and tumor volume and weight were measured. The expression of SMP-30 was detected in laminarin-treated Bel-7404 and HepG2 HCC cells and LO2 normal liver cells by quantitative real-time PCR and Western blotting. Results: The treatment with laminarin (48 h) significantly decreased the viability and increased the apoptosis rates of Bel-7404 and HepG2 cells in a dose-dependent manner. The injection of laminarin also significantly decreased the tumor volumes (beginning on the 10th day) and tumor weights (30 d post-injection) of mice in a dose-dependent manner. In addition, the treatment with laminarin (35 mg/mL for 48 h) significantly upregulated SMP-30 in Bel-7404 and HepG2 cells but not in LO2 cells. Conclusion: Laminarin inhibited the proliferation of Bel-7404 and HepG2 cells and inhibited the growth of tumors in Hepa 1–6 tumor-bearing mice by upregulating SMP-30.
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Affiliation(s)
- Lin Tian
- School of Preclinical Medicine, Guangxi Medical University, Nanning, China.,Science and Technology College, Hubei Minzu University, Enshi, China
| | - Chun-Mei Li
- School of Preclinical Medicine, Guangxi Medical University, Nanning, China.,Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Yan-Fei Li
- School of Preclinical Medicine, Guangxi Medical University, Nanning, China
| | - Tian-Ming Huang
- School of Preclinical Medicine, Guangxi Medical University, Nanning, China
| | - Nai-Xia Chao
- School of Preclinical Medicine, Guangxi Medical University, Nanning, China
| | - Guo-Rong Luo
- School of Preclinical Medicine, Guangxi Medical University, Nanning, China.,Guangxi Colleges and Universities Key Laboratory of Human Development and Disease Research, Guangxi Medical University, Nanning, China
| | - Fa-Rong Mo
- School of Preclinical Medicine, Guangxi Medical University, Nanning, China.,Guangxi Colleges and Universities Key Laboratory of Human Development and Disease Research, Guangxi Medical University, Nanning, China
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18
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Qian S, Golubnitschaja O, Zhan X. Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles. EPMA J 2019; 10:365-381. [PMID: 31832112 PMCID: PMC6882964 DOI: 10.1007/s13167-019-00194-x] [Citation(s) in RCA: 131] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 11/06/2019] [Indexed: 12/24/2022]
Abstract
A strong relationship exists between tumor and inflammation, which is the hot point in cancer research. Inflammation can promote the occurrence and development of cancer by promoting blood vessel growth, cancer cell proliferation, and tumor invasiveness, negatively regulating immune response, and changing the efficacy of certain anti-tumor drugs. It has been demonstrated that there are a large number of inflammatory factors and inflammatory cells in the tumor microenvironment, and tumor-promoting immunity and anti-tumor immunity exist simultaneously in the tumor microenvironment. The typical relationship between chronic inflammation and tumor has been presented by the relationships between Helicobacter pylori, chronic gastritis, and gastric cancer; between smoking, development of chronic pneumonia, and lung cancer; and between hepatitis virus (mainly hepatitis virus B and C), development of chronic hepatitis, and liver cancer. The prevention of chronic inflammation is a factor that can prevent cancer, so it effectively inhibits or blocks the occurrence, development, and progression of the chronic inflammation process playing important roles in the prevention of cancer. Monitoring of the causes and inflammatory factors in chronic inflammation processes is a useful way to predict cancer and assess the efficiency of cancer prevention. Chronic inflammation-based biomarkers are useful tools to predict and prevent cancer.
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Affiliation(s)
- Shehua Qian
- 1Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 2Hunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 3State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
| | - Olga Golubnitschaja
- 4Radiological Clinic, UKB, Excellence Rheinische Friedrich-Wilhelms-University of Bonn, Sigmund-Freud-Str 25, 53105 Bonn, Germany
- 5Breast Cancer Research Centre, UKB, Excellence Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany
- 6Centre for Integrated Oncology, Cologne-Bonn, Excellence Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany
| | - Xianquan Zhan
- 1Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 2Hunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 3State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 7Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan People's Republic of China
- 8National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan People's Republic of China
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19
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Zhang H, Chen X, Zhang J, Wang X, Chen H, Liu L, Liu S. Long non‑coding RNAs in HBV‑related hepatocellular carcinoma (Review). Int J Oncol 2019; 56:18-32. [PMID: 31746420 DOI: 10.3892/ijo.2019.4909] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 09/02/2019] [Indexed: 12/25/2022] Open
Abstract
Hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC) is a global health problem that accounts for more than half of total liver cancer cases in developing countries. Despite the growing number of researches conducted, the molecular mechanism underlying the development of HCC remains elusive. Long non‑coding RNAs (lncRNAs), which are non‑coding RNAs >200 nt in length that were previously considered to be transcriptional noise, have been found to be dysregulated in HBV‑related HCC with the help of high‑throughput omics techniques. Subsequent investigations revealed that aberrant expression of lncRNAs may affect the risk of HBV‑related HCC through diverse mechanisms, including epigenetic silencing of transcriptional activation, alternative splicing, molecular sponging, modulating protein stability, and by serving as precursors of miRNAs. Although the sensitivity and specificity of lncRNAs must be further validated, a number of circulating lncRNAs have been identified as useful biomarkers for HBV‑related HCC. In addition to these findings, recent studies also unveiled that certain genetic polymorphisms in lncRNAs may affect the occurrence and prognosis of HBV‑related HCC. The aim of the present review was to provide an overview of the mechanisms underlying the involvement of lncRNAs in HBV‑related HCC. Subsequently, lncRNAs found to be dysregulated in HBV‑related HCC were focused on and current findings on circulating lncRNAs and their genetic polymorphisms were discussed.
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Affiliation(s)
- Hao Zhang
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Sichuan 610000, P.R. China
| | - Xuebing Chen
- Department of Infectious Diseases, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Jian Zhang
- Department of Pathology, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Xianwei Wang
- Department of Pathology, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Huijuan Chen
- Department of Pathology, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Lin Liu
- Department of Pathology, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
| | - Shanling Liu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Sichuan 610000, P.R. China
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20
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Xu Q, Shi NJ, Zhang H, Zhu YM. Effects of combined general-epidural anesthesia and total intravenous anesthesia on cellular immunity and prognosis in patients with non‑small cell lung cancer: A comparative study. Mol Med Rep 2017; 16:4445-4454. [PMID: 28765974 PMCID: PMC5647004 DOI: 10.3892/mmr.2017.7144] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Accepted: 05/04/2017] [Indexed: 12/16/2022] Open
Abstract
The aim of the present study was to investigate the effects of combined general-epidural anesthesia (CGEA) and total intravenous anesthesia (TIVA) on cellular immunity and prognosis in patients with non-small cell lung cancer (NSCLC) in a Chinese population. One-hundred and twenty NSCLC patients were randomly divided into a TIVA group (n=60) and a CGEA group (n=60) using a random number table. All patients underwent video-assisted thoracoscopic surgery for radical resection. Blood pressure (BP) and peripheral oxygen saturation (SpO2) were measured. Post-operative analgesic effects were evaluated with a visual analog scale pain score. Flow cytometry was applied to measure T lymphocyte subsets [cluster of differentiation (CD)3+, CD4+, CD8+ and CD4+/CD8+] and natural killer cell CD56+. A 3-year follow-up was conducted to observe the prognosis. The analgesic effects of CGEA were identified to be better than those of TIVA. Compared with the TIVA group, the CGEA group demonstrated a shorter time of spontaneous breathing recovery, eyes opening, and extubation, lower heart rate, blood pressure and mean arterial pressure, and higher SpO2. At 24 and 48 h after surgery, CD3+, CD4+, CD4+/CD8+ and CD56+ in the CGEA group were higher than those in the TIVA group. At 72 h after surgery, CD3+, CD4+, CD4+/CD8+ in the CGEA group were higher than those in the TIVA group. These results indicate that CGEA and TIVA effected cellular immunity, and CGEA had a reduced effect on cellular immunity and improved postoperative analgesic effects.
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Affiliation(s)
- Qiang Xu
- Department of Anesthesiology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Nian-Jun Shi
- Department of Anesthesiology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Hao Zhang
- Department of Anesthesiology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Yan-Mei Zhu
- Department of Orthopedics, Chinese Medicine Hospital in Linyi, Linyi, Shandong 276003, P.R. China
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21
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Abstract
Hepatocellular carcinoma (HCC) is the predominant primary liver cancer in many countries and is the third most common cause of cancer-related death in the Asia-Pacific region. The incidence of HCC is higher in men and in those over 40 years old. In the Asia-Pacific region, chronic hepatitis B virus and hepatitis C virus infections are the main etiological agents; in particular, chronic hepatitis B infection (CHB) is still the major cause in all Asia-Pacific countries except for Japan. Over the past two decades, the incidence of HCC has remained stable in countries in the region except for Singapore and Hong Kong, where the incidence for both sexes is currently decreasing. Chronic hepatitis C infection (CHC) is an important cause of HCC in Japan, representing 70% of HCCs. Over the past several decades, the prevalence of CHC has been increasing in many Asia-Pacific countries, including Australia, New Zealand, and India. Despite advancements in treatment, HCC is still an important health problem because of the associated substantial mortality. An effective surveillance program could offer early diagnosis and hence better treatment options. Antiviral treatment for both CHB and CHC is effective in reducing the incidence of HCC.
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Affiliation(s)
- Ran Xu Zhu
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Ching-Lung Lai
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Man-Fung Yuen
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
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22
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Wang M, Xi D, Ning Q. Virus-induced hepatocellular carcinoma with special emphasis on HBV. Hepatol Int 2017; 11:171-180. [PMID: 28097530 DOI: 10.1007/s12072-016-9779-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 12/22/2016] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is a common malignant tumor with high lethality, and the hepatitis B virus (HBV) is a chief cause. HBV can accelerate HCC via multiple mechanisms. First, HBV induces immune reactions that lead to repeated hepatic inflammation, fibrosis and a deficient immune microenvironment. Subsequently, HBV can modify host genes near the insertion point through DNA integration to cause host cell genome instability and to generate carcinogenic fusion proteins. Additionally, HBV expresses diverse active proteins, especially HBx and HBs, which have a range of transactivation functions such as regulation of apoptosis, interference with intracellular signaling pathways, and alteration of epigenetics. Currently, primary prevention measures for HBV-induced HCC focus on vaccination and antiviral treatment. Here, we report the epidemiology, the molecular mechanism and the progress in therapeutic strategies for controlling HBV-induced HCC.
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Affiliation(s)
- Ming Wang
- Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No 1095, Jiefang Avenue, Wuhan, 430030, China
| | - Dong Xi
- Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No 1095, Jiefang Avenue, Wuhan, 430030, China
| | - Qin Ning
- Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No 1095, Jiefang Avenue, Wuhan, 430030, China.
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M Hussain M, Al Mahtab M, Islam S, Ahmed N, Rahman S, Khan M. Relationship between Hepatitis B Viral Deoxyribonucleic Acid Load and Hepatocellular Carcinoma. Euroasian J Hepatogastroenterol 2017; 7:111-112. [PMID: 29201789 PMCID: PMC5663791 DOI: 10.5005/jp-journals-10018-1228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Accepted: 11/10/2016] [Indexed: 11/23/2022] Open
Abstract
Introduction: Hepatitis B virus (HBV) infection is an established cause of hepatocellular carcinoma (HCC) and is associated with poor prognosis. High HBV deoxyribonucleic acid (DNA) load has been identified in HCC and hepatitis B surface antigen-positive patients. Materials and methods: This study was done in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from January 2006 to December 2007. Thirty patients with HBV infection-related HCC were enrolled. Another 30 patients with HBV-related liver diseases without HCC were analyzed as controls. Results: The HCC patients had a high viral load (>105 copies/mL), while all of the controls had low (<105 copies/mL) viral load. Conclusion: It seems that patients with HCC bear high HBV DNA loads in Bangladesh, but the causes underlying this remain to be resolved. How to cite this article: Hussain MM, Al Mahtab M, Islam S, Ahmed N, Rahman S, Khan M. Relationship between Hepatitis B Viral Deoxyribonucleic Acid Load and Hepatocellular Carcinoma. Euroasian J Hepato-Gastroenterol 2017;7(1):111-112.
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Affiliation(s)
- Muhammad M Hussain
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shahidul Islam
- Department of Oncology Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Nooruddin Ahmed
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Salimur Rahman
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Mobin Khan
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
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24
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Regulatory T-cells promote hepatitis B virus infection and hepatocellular carcinoma progression. Chronic Dis Transl Med 2016; 2:67-80. [PMID: 29063027 PMCID: PMC5643754 DOI: 10.1016/j.cdtm.2016.09.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Indexed: 02/08/2023] Open
Abstract
Regulatory T-cells (Tregs), known for their immune suppressive function, have been reported in higher numbers, with activated phenotypes and greater potency, in hepatitis B virus (HBV)-related liver diseases than in normal conditions. The numbers, phenotypes, and function of intrahepatic and/or tumor-infiltrating Tregs in HBV-related liver diseases also differ from those of Tregs in the peripheral blood. By inhibiting the function of effector T-cells (Teffs), Tregs play a substantial role in the formation and maintenance of the liver's suppressive microenvironment, which might account for the progression of HBV-related hepatitis and hepatocellular carcinoma (HCC). In acute hepatitis B virus infection, Tregs can safeguard the liver from damage at the cost of prolonged antiviral processes, which results in chronic HBV infection in the liver. Furthermore, Tregs play a role in the development of cirrhosis, the transformation of cirrhosis to HCC, and the progression and metastasis of HCC. Higher levels of Tregs in the peripheral blood and/or tumor sites signify a poorer prognosis in HBV-related liver conditions, and observational data from mouse models and human patients support the theory that depleting Tregs may be therapeutic in HBV-related liver diseases by inducing antiviral and antitumor immunity.
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25
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Makvandi M. Update on occult hepatitis B virus infection. World J Gastroenterol 2016; 22:8720-8734. [PMID: 27818588 PMCID: PMC5075547 DOI: 10.3748/wjg.v22.i39.8720] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/13/2016] [Accepted: 07/20/2016] [Indexed: 02/06/2023] Open
Abstract
The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world.
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26
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Du Y, Han X, Ding YB, Yin JH, Cao GW. Prediction and prophylaxis of hepatocellular carcinoma occurrence and postoperative recurrence in chronic hepatitis B virus-infected subjects. World J Gastroenterol 2016; 22:6565-6572. [PMID: 27547000 PMCID: PMC4970480 DOI: 10.3748/wjg.v22.i29.6565] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 06/10/2016] [Accepted: 06/28/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and highly fatal malignancies worldwide. Chronic infection with hepatitis B virus (HBV) is a major cause of HCC. High HBV replication rate and related non-resolving inflammation are the major risk factors of HCC occurrence and postoperative recurrence. Early prophylactic options are effective in reducing HCC occurrence and improving survival. Therefore, it is important to identify HBV-infected patients who are at a higher risk of developing HCC and HBV-HCC patients who are more likely to relapse after surgery, thus providing them with more precise prophylactic strategies. Several prediction models of HCC occurrence have been constructed, with satisfactory predictive accuracy and discriminatory ability. However, there is a lack of consensus for their clinical implementation. Several staging systems have been proposed for HCC prognosis. However, the accuracy of these staging systems based on demographic characteristics and clinical measurements needs to be further improved, possibly by systematically incorporating viral and inflammatory factors. Since antiviral treatments are effective in promoting liver function reserve, reducing HCC occurrence and prolonging postoperative survival in some HBV-infected subjects, it is very important to identify subgroups of HBV-infected patients who would most benefit from antiviral treatment.
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27
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Wu Y, Zhang J, Zhang H, Zhai Y. Hepatitis B virus X protein mediates yes-associated protein 1 upregulation in hepatocellular carcinoma. Oncol Lett 2016; 12:1971-1974. [PMID: 27602122 DOI: 10.3892/ol.2016.4885] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Accepted: 07/04/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) X protein (HBx) is implicated in the development of hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP) is an important proto-oncogene, which is a downstream effector molecule in the Hippo signaling pathway. The aim of the present study was to investigate the association between HBx expression in HCC samples and YAP expression in the Hippo pathway. A total of 20 pathologically confirmed HCC samples, 20 corresponding adjacent non-tumor liver tissues and 5 normal liver tissue samples were collected. The expression of HBx and YAP in the tissues was analyzed by quantitative reverse transcription-polymerase chain reaction and western blot analysis. The intensity and location of YAP expression were analyzed by immunohistochemistry. YAP mRNA and protein expression levels in HCC samples infected with HBV were significantly higher than those of normal liver tissues. Furthermore, YAP expression was positively correlated with HBx expression in HBV-positive HCC samples. Immunohistochemical staining revealed that YAP was predominantly expressed in the nuclei in HBV-positive HCC tissues. YAP expression was significantly decreased in the normal liver tissue and corresponding adjacent liver tissue when compared with the HCC tissues and by contrast to HCC tissues, YAP was predominantly located in the cytoplasm. In conclusion, these results indicate that the YAP gene is a key driver of HBx-induced liver cancer. Therefore, YAP may present a novel target in the treatment of HBV-associated HCC.
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Affiliation(s)
- Yuzhuo Wu
- Department of Infectious Diseases, Nanyang City Central Hospital, Nanyang, Henan 473000, P.R. China
| | - Junhe Zhang
- Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
| | - Huaihong Zhang
- Department of Infectious Diseases, Nanyang City Central Hospital, Nanyang, Henan 473000, P.R. China
| | - Yufeng Zhai
- Department of Infectious Diseases, Nanyang City Central Hospital, Nanyang, Henan 473000, P.R. China
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28
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Song C, Liu Y, Xu L, Wen J, Jiang D, Chen J, Zhai X, Hu Z, Liu L, Liu J. Hepatitis B virus mutations, expression quantitative trait loci for PTPN12, and their interactions in hepatocellular carcinoma. Cancer Med 2016; 5:1687-1693. [PMID: 27075395 PMCID: PMC4944896 DOI: 10.1002/cam4.712] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 02/29/2016] [Accepted: 03/01/2016] [Indexed: 12/11/2022] Open
Abstract
Previously we identified that HBV(Hepatitis B virus) sequence variation, which may interact with host human leukocyte antigen (HLA) genetic variation, could influence host risk of hepatocellular carcinoma (HCC). More HBV-host interactions need to be identified. Protein tyrosine phosphatase nonreceptor type 12 (PTPN12), serves as an antagonist to tyrosine kinase signaling, may play integral roles in immune response against HBV infection and the development of HCC. Rs11485985 was an expression quantitative trait loci (eQTL) for PTPN12 by bioinformatics analyses. In this study, we genotyped the PTPN12 eQTL and sequenced the HBV region EnhII/BCP/PC in a case-control cohort including 1507 HBV-related HCC cases and 1560 HBV persistent carriers as controls. The variant genotype GG of rs11489585 increased HCC risk compared to the HBV persistent carriers (adjusted OR = 2.03, 95% confidence interval [CIs] = 1.30-3.18). We also detected borderline significant associations of PTPN12 eQTL rs11489585 with HBV mutations (P = 0.05 for G1799C). Taken together, PTPN12 may influence HCC risk accompanied by HBV mutations.
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Affiliation(s)
- Ci Song
- Department of EpidemiologyCollaborative Innovation Center For Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjing211166China
- Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center of Cancer MedicineNanjing Medical UniversityNanjing211166China
| | - Yao Liu
- Pathology Center and Department of PathologySoochow UniversitySuzhouChina
| | - Lu Xu
- Department of EpidemiologyCollaborative Innovation Center For Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjing211166China
| | - Juan Wen
- Nanjing Maternity and Child Health Care InstituteNanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical UniversityNanjingChina
| | - Deke Jiang
- State Key Laboratory of Genetic EngineeringCollaborative Innovation Center for Genetics and DevelopmentSchool of Life SciencesFudan UniversityShanghaiChina
| | | | - Xiangjun Zhai
- Department of Infection DiseasesJiangsu Province Center for Disease Prevention and ControlNanjingChina
| | - Zhibin Hu
- Department of EpidemiologyCollaborative Innovation Center For Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjing211166China
- Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center of Cancer MedicineNanjing Medical UniversityNanjing211166China
| | - Li Liu
- Digestive Endoscopy Centerthe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Jibin Liu
- Department of Hepatobiliary SurgeryNantong Tumor HospitalNantongChina
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29
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Liu WB, Wu JF, Du Y, Cao GW. Cancer Evolution-Development: experience of hepatitis B virus-induced hepatocarcinogenesis. ACTA ACUST UNITED AC 2016; 23:e49-56. [PMID: 26966413 DOI: 10.3747/co.23.2836] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Here, we present the basic concept and theoretical framework of a scientific hypothesis called Cancer Evolution-Development ("Cancer Evo-Dev"), based on our recent studies of the molecular mechanisms by which chronic infection with the hepatitis B virus induces hepatocarcinogenesis, together with related advances in that field. Several aspects central to our hypothesis are presented: ■ Immune imbalance-caused by the interaction of genetic predispositions and environmental exposures such as viral infection-is responsible for the maintenance of chronic non-resolving inflammation. Non-resolving inflammation promotes the occurrence and progression of cancers, characterized by an evolutionary process of "mutation-selection-adaptation" for both viruses and host cells.■ Under a microenvironment of non-resolving inflammation, proinflammatory factors promote mutations in viral or host genomes by transactivation of the expression of cytidine deaminases and their analogues. Most cells with genomic mutations and mutated viruses are eliminated in the competition for survival in the inflammatory microenvironment. Only a small percentage of the mutated cells that alter their survival signal pathways and exhibit the characteristics of "stem-ness" can survive and function as cancer-initiating cells.■ Cancers generally develop with properties of "backward evolution" and "retro-differentiation," indicating the indispensability of stem-like signal pathways in the evolution and development of cancers. The hypothesis of Cancer Evo-Dev not only lays the theoretical foundation for understanding the mechanisms by which inflammation promotes the development of cancers, but also plays an important role in specific prophylaxis, prediction, early diagnosis, and targeted treatment of cancers.
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Affiliation(s)
- W B Liu
- Department of Epidemiology, Second Military Medical University, Shanghai, P.R.C
| | - J F Wu
- Department of Epidemiology, Second Military Medical University, Shanghai, P.R.C
| | - Y Du
- Department of Epidemiology, Second Military Medical University, Shanghai, P.R.C
| | - G W Cao
- Department of Epidemiology, Second Military Medical University, Shanghai, P.R.C
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30
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Wei D, Zeng Y, Xing X, Liu H, Lin M, Han X, Liu X, Liu J. Proteome Differences between Hepatitis B Virus Genotype-B- and Genotype-C-Induced Hepatocellular Carcinoma Revealed by iTRAQ-Based Quantitative Proteomics. J Proteome Res 2016; 15:487-98. [PMID: 26709725 DOI: 10.1021/acs.jproteome.5b00838] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Hepatitis B virus (HBV) is the main cause of hepatocellular carcinoma (HCC) in southeast Asia where HBV genotype B and genotype C are the most prevalent. Viral genotypes have been reported to significantly affect the clinical outcomes of HCC. However, the underlying molecular differences among different genotypes of HBV virus infected HCC have not been revealed. Here, we applied isobaric tags for relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify the proteome differences between the HBV genotypes B- and C-induced HCC. In brief, a total of 83 proteins in the surrounding noncancerous tissues and 136 proteins in the cancerous tissues between HBV genotype-B- and genotype-C-induced HCC were identified, respectively. This information revealed that there might be different molecular mechanisms of the tumorigenesis and development of HBV genotypes B- and C-induced HCC. Furthermore, our results indicate that the two proteins ARFIP2 and ANXA1 might be potential biomarkers for distinguishing the HBV genotypes B- and C-induced HCC. Thus, the quantitative proteomic analysis revealed molecular differences between the HBV genotypes B- and C-induced HCC, and might provide fundamental information for further deep study.
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Affiliation(s)
- Dahai Wei
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University , Fuzhou 350025, People's Republic of China
| | - Yongyi Zeng
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University , Fuzhou 350025, People's Republic of China.,Liver Disease Center, The First Affiliated Hospital of Fujian Medical University , Fuzhou 350007, People's Republic of China
| | - Xiaohua Xing
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University , Fuzhou 350025, People's Republic of China
| | - Hongzhi Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University , Fuzhou 350025, People's Republic of China
| | - Minjie Lin
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University , Fuzhou 350025, People's Republic of China
| | - Xiao Han
- Biotechnology Research Institute, Chinese Academy of Agricultural Sciences , Beijing 100081, People's Republic of China
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University , Fuzhou 350025, People's Republic of China
| | - Jingfeng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University , Fuzhou 350025, People's Republic of China.,Liver Disease Center, The First Affiliated Hospital of Fujian Medical University , Fuzhou 350007, People's Republic of China
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31
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Hou Q, Duan ZJ. Metabonomic window into hepatitis B virus-related hepatic diseases. World J Hepatol 2016; 8:1-8. [PMID: 26783418 PMCID: PMC4705451 DOI: 10.4254/wjh.v8.i1.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 09/15/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023] Open
Abstract
Metabonomics has recently been widely used to discover the pathogenesis and find potential metabolic markers with high sensitivity and specificity. Furthermore, it develops new diagnosis and treatment methods, increases early phase diagnosis rates of certain diseases and provides a new basis for targeted therapy. This review mainly analyzes the research progress of the metabonomics of hepatitis B virus (HBV)-related hepatic diseases, hoping to discover some potential metabolic markers for identification of HBV-related hepatic diseases from other etiologies and for HBV-related hepatitis, liver cirrhosis and hepatocellular carcinoma. This can contribute to early discovery, diagnosis and treatment, eventually increasing the survival rate of HBV-related hepatic diseases.
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32
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Loustaud-Ratti V, Jacques J, Debette-Gratien M, Carrier P. Hepatitis B and elders: An underestimated issue. Hepatol Res 2016; 46:22-8. [PMID: 25651806 DOI: 10.1111/hepr.12499] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 01/17/2015] [Accepted: 02/02/2015] [Indexed: 12/16/2022]
Abstract
As the world's population becomes older, the burden of hepatitis B virus in elderly has to be considered. The liver changes with aging and its function is eventually altered. The prevalence of hepatitis B virus is paradoxically more important in elderly in areas having vaccination programs, because of a loosening of the prevention in older patients. Some differences in hepatitis B presentation must be enhanced in elderly: lower spontaneous hepatitis B surface antigen clearance after a recent contamination, major risk of cirrhosis and hepatocarcinoma. Acute hepatitis B seems to be more often symptomatic, with a great risk of chronicity. Hepatocarcinoma linked to hepatitis B virus has a higher prevalence and a different presentation in elderly. Its treatment is the same as in younger people but is less often possible. Liver transplantation is contraindicated after 70 years old. Hepatitis B treatment panel is the same as in younger people (pegylated interferon, nucleoside or nucleotide agents). It gives identical results with no particular adverse events if the precautions for use are followed. Vaccination is less efficient, as in immunocompromised patients, and needs specific protocols.
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Affiliation(s)
- Véronique Loustaud-Ratti
- Federation of Hepatology, Gastroenterology and Hepatology Unit, CHU Limoges.,INSERM UMR 850, School of Medicine, Limoges, France
| | - Jérémie Jacques
- Federation of Hepatology, Gastroenterology and Hepatology Unit, CHU Limoges
| | | | - Paul Carrier
- Federation of Hepatology, Gastroenterology and Hepatology Unit, CHU Limoges
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33
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Chen Jr MS, Dang J. Hepatitis B among Asian Americans: Prevalence, progress, and prospects for control. World J Gastroenterol 2015; 21:11924-30. [PMID: 26576081 PMCID: PMC4641114 DOI: 10.3748/wjg.v21.i42.11924] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 06/18/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
After tobacco use, chronic hepatitis B (CHB) viral infections are the most important cause of cancer globally in that 1 out of 3 individuals have been infected with the hepatitis B virus (HBV). Though infection rates are low (< 1%) in the United States, Asian Americans who comprise about 6% of the population experience about 60% of the CHB burden. This paper reviews the magnitude of hepatitis B (HBV) burden among Asian Americans and the progress being made to mitigate this burden, primarily through localized, community-based efforts to increase screening and vaccination among Asian American children, adolescents, and adults. This review brings to light that despite the numerous community-based screening efforts, a vast majority of Asian Americans have not been screened and that vaccination efforts, particularly for adults, are sub-optimal. Greater efforts to integrate screenings by providers within existing healthcare systems are urged. Evidence-based strategies are offered to implement CDC's three major recommendations to control and prevent hepatitis B through targeted screening and enhanced vaccination efforts.
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34
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Zhang X, Zhu S, Zhu W, Li A, Zhu N. A Newly Identified Natural Splice Variant ASN Enhances Hepatitis B Virus Amplification. Viral Immunol 2015; 29:27-32. [PMID: 26501888 DOI: 10.1089/vim.2015.0044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection causes approximately one-third of all the cases of liver cirrhosis and more than three-quarters of hepatocellular carcinoma (HCC) worldwide. There are eight different genotypes (A-H) of HBV, among which B and C are the major types of HBV in China. There is a positive correlation between viral load and level of viral splicing variants and the high risk of HCC. The aim of this study was to investigate the splicing variants of HBV circulating in HCC patients. Twenty-four carcinoma and adjacent liver tissues collected from HCC patients were studied. Using reverse transcription-polymerase chain reaction (RT-PCR) and sequencing, we identified a new type of natural splice variant with nucleotides 2448-489 and 910-2120 deleted, and we named it ASN. We also found that a higher viral load and splicing variant level existed in liver carcinoma tissues compared to paracarcinoma tissues. In the investigation of our splicing variant, we found its enhancing effect on HBV replication in vitro. Although splicing variants are not essential for the replication of HBV, they may have an important influence.
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Affiliation(s)
- Xiumin Zhang
- 1 Lab of Molecular Immunology, State Key Lab of Genetic Engineering, Institute of Biomedical Sciences (IBS), School of Life Sciences, Fudan University , Shanghai, People's Republic of China
| | - Sibo Zhu
- 1 Lab of Molecular Immunology, State Key Lab of Genetic Engineering, Institute of Biomedical Sciences (IBS), School of Life Sciences, Fudan University , Shanghai, People's Republic of China
| | - Wei Zhu
- 1 Lab of Molecular Immunology, State Key Lab of Genetic Engineering, Institute of Biomedical Sciences (IBS), School of Life Sciences, Fudan University , Shanghai, People's Republic of China
| | - Aijun Li
- 2 Oriental Liver Surgery Hospital, Second Military Medical University , Shanghai, People's Republic of China
| | - Naishuo Zhu
- 1 Lab of Molecular Immunology, State Key Lab of Genetic Engineering, Institute of Biomedical Sciences (IBS), School of Life Sciences, Fudan University , Shanghai, People's Republic of China
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35
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Woo JH, Baik HJ, Kim CH, Chung RK, Kim DY, Lee GY, Chun EH. Effect of Propofol and Desflurane on Immune Cell Populations in Breast Cancer Patients: A Randomized Trial. J Korean Med Sci 2015; 30:1503-8. [PMID: 26425050 PMCID: PMC4575942 DOI: 10.3346/jkms.2015.30.10.1503] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 06/10/2015] [Indexed: 01/21/2023] Open
Abstract
Several factors can affect the perioperative immune function. We evaluated the effect of propofol and desflurane anesthesia on the surgery-induced immune perturbation in patients undergoing breast cancer surgery. The patients were randomly assigned to receive propofol (n = 20) or desflurane (n = 20) anesthesia. The total and differential white blood cell counts were determined with lymphocyte subpopulations before and 1 hr after anesthesia induction and at 24 hr postoperatively. Plasma concentrations of interleukin (IL)-2 and IL-4 were also measured. Both propofol and desflurane anesthesia preserved the IL-2/IL-4 and CD4(+)/CD8(+) T cell ratio. Leukocytes were lower in the propofol group than in the desflurane group at 1 hr after induction (median [quartiles], 4.98 [3.87-6.31] vs. 5.84 [5.18-7.94] 10(3)/µL) and 24 hr postoperatively (6.92 [5.54-6.86] vs. 7.62 [6.22-9.21] 10(3)/µL). NK cells significantly decreased 1 hr after induction in the propofol group (0.41 [0.34-0.53] to 0.25 [0.21-0.33] 10(3)/µL), but not in the desflurane group (0.33 [0.29-0.48] to 0.38 [0.30-0.56] 10(3)/µL). Our findings indicate that both propofol and desflurane anesthesia for breast cancer surgery induce a favorable immune response in terms of preservation of IL-2/IL-4 and CD4(+)/CD8(+) T cell ratio in the perioperative period. With respect to leukocytes and NK cells, desflurane anesthesia is associated with less adverse immune responses than propofol anesthesia during surgery for breast cancer. (Clinical trial registration at https://cris.nih.go.kr/cris number: KCT0000939).
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Affiliation(s)
- Jae Hee Woo
- Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Hee Jung Baik
- Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Chi Hyo Kim
- Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Rack Kyung Chung
- Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Dong Yeon Kim
- Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Guie Yong Lee
- Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Eun Hee Chun
- Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, Seoul, Korea
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Hong DF, Liu YB, Peng SY, Pang JZ, Wang ZF, Cheng J, Shen GL, Zhang YB. Management of hepatocellular carcinoma rupture in the caudate lobe. World J Gastroenterol 2015; 21:8163-8169. [PMID: 26185390 PMCID: PMC4499361 DOI: 10.3748/wjg.v21.i26.8163] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Revised: 02/22/2015] [Accepted: 04/28/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To demonstrate that caudate lobectomy is a valid treatment in cases of hepatocellular carcinoma (HCC) rupture in the caudate lobe based on our experience with the largest case series reported to date. METHODS A retrospective study of eight patients presenting with spontaneous rupture and hemorrhage of HCC in the caudate lobe was conducted. Two patients underwent ineffective transarterial embolization preoperatively. Caudate lobectomy was performed in all eight patients. Bilateral approach was taken in seven cases for isolated complete caudate lobectomy. Left-sided approach was employed in one case for isolated partial caudate lobectomy. Transarterial chemoembolization was performed postoperatively in all patients. RESULTS Caudate lobectomy was successfully completed in all eight cases. The median time delay from the diagnosis to operation was 5 d (range: 0.25-9). Median operating time was 200 min (range: 120-310) with a median blood loss of 900 mL (range: 300-1500). Five patient remained in long-term follow-up, with one patient becoming lost to follow-up at 3 years and two patients currently alive at 7 and 19 mo. One patient required reoperation due to recurrence. Gamma knife intervention was performed for brain metastasis in another case. Two patients survived for 10 and 84 mo postoperatively, ultimately succumbing to multiple organ metastases. CONCLUSION Caudate lobectomy is the salvage choice for HCC rupture in the caudate lobe. Local anatomy and physiologic features of the disease render caudate lobectomy a technically difficult operation. Postponement of surgical intervention is thus recommended while the rupture remains hemodynamically stable until an experienced surgeon becomes available. Prognosis is confounded by numerous factors, but long-term survival can be expected in the majority of cases.
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Li C, Wang J, Zhang H, Zhu M, Chen F, Hu Y, Liu H, Zhu H. Interferon-stimulated gene 15 (ISG15) is a trigger for tumorigenesis and metastasis of hepatocellular carcinoma. Oncotarget 2015; 5:8429-41. [PMID: 25238261 PMCID: PMC4226694 DOI: 10.18632/oncotarget.2316] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with poor prognosis. IFN-stimulated genes 15 (ISG15) is an ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. However, the role of ISG15 in HCC remains unclear. In this study, we investigated the function of ISG15 during HCC progression and related mechanism using clinicopathological data, cell line and xenograft model. Our results indicated that ISG15 is highly expressed in HCC tissues and multiple HCC cell lines. ISG15 expression is significantly associated with the differentiation grade, metastatic of tumor and survival of HCC patients. However, the expression of ISG15 is not affected by HBV infection. ISG15 promotes the proliferation and migration of hepatocarcinoma cells through maintaining Survivin protein stabilization via sequestering XIAP from interacting with Survivin. Knowing down ISG15 with SiRNA inhibited the xenografted tumor growth and prolonged the lifespan of tumor-bearing mice. All these results support that ISG15 high expression is an intrinsic feature for HCC and a trigger for tumorigenesis and metastasis. ISG15 may be a prognostic biomarker and the inhibition of ISG15 could provide a therapeutic advantage for HCC patients over-expressing ISG15.
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Affiliation(s)
- Chong Li
- Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China. CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences (CAS), Beijing, China
| | - Ji Wang
- Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Hong Zhang
- Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Mingao Zhu
- Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Feifei Chen
- Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yufeng Hu
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hudan Liu
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hong Zhu
- Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, China
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Preoperative serum liver enzyme markers for predicting early recurrence after curative resection of hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2015; 14:178-85. [PMID: 25865691 DOI: 10.1016/s1499-3872(15)60353-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Early recurrence of hepatocellular carcinoma (HCC) is associated with worse prognosis after liver resection. This study aimed to investigate the prognostic value of common liver enzyme markers in HCC early recurrence after curative hepatectomy and to establish a simple predictive model for HCC early recurrence. METHODS A total of 200 patients who had undergone curative resection for HCC were retrospectively analyzed. The patients were divided into early recurrence (within 2 years) and non-early recurrence groups. Demographical characteristics, preoperative liver function parameters, surgical factors and tumor related factors of the patients were assessed by univariate analysis to identify potential significant predictors for early recurrence after resection of HCC. Parameters with statistical significance were entered into a Cox proportional hazard model to find independent risk factors. Receiver operating characteristic analysis was done to determine optimal cut-off values and the number of combined factors in multi-factor predictive model. RESULTS Of 13 potential risk factors for early recurrence identified by univariate analysis, high lactate dehydrogenase (LDH>206 U/L, HR=1.711, P=0.006), high aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AST/ALT>0.96, HR=1.769, P=0.006), elevated alpha-fetoprotein (AFP<8.6 ng/mL, HR=2.079, P=0.007), small resection margin (≤1 cm, HR=2.354, P<0.001) and advanced TNM stage (TNM III-IV, HR=2.164, P<0.001) were independent risk factors for early recurrence of HCC shown by multivariate analysis. Patients with three or more concurrent independent risk factors had significantly higher risk for early recurrence than those with low risk factors. The sensitivity and specificity of this predictive model are 53.6% and 80.7%, respectively (area under curve=0.741, 95% CI 0.674-0.800, P<0.0001). CONCLUSIONS Preoperative common liver enzyme markers, LDH and AST/ALT ratio, were independently associated with early recurrence of HCC. The combination of serum liver enzyme markers with AFP, resection margin and TNM stage better predicted early recurrence of HCC after curative resection in a simple multi-factor model.
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Zhou L, Lu L, Wicha MS, Chang AE, Xia JC, Ren X, Li Q. Promise of cancer stem cell vaccine. Hum Vaccin Immunother 2015; 11:2796-9. [PMID: 26337078 PMCID: PMC5054775 DOI: 10.1080/21645515.2015.1083661] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Revised: 07/27/2015] [Accepted: 08/11/2015] [Indexed: 12/19/2022] Open
Abstract
Dendritic cell (DC)-based vaccines designed to target cancer stem cells (CSC) can induce significant antitumor responses via conferring host anti-CSC immunity. Our recent studies have demonstrated that CSC-DC vaccine could inhibit metastasis of primary tumors and induce humoral immune responses against cancer stem cells. This approach highlights the promise of cancer stem cell vaccine in cancer immunotherapy.
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Affiliation(s)
- Li Zhou
- Comprehensive Cancer Center; University of Michigan; Ann Arbor, MI USA
- Department of Biotherapy; Tianjin University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Immunology and Biotherapy; Tianjin, China
| | - Lin Lu
- Comprehensive Cancer Center; University of Michigan; Ann Arbor, MI USA
- State Key Laboratory of Oncology in Southern China and Department of Experimental Research; Sun Yat-sen University Cancer Center; Guangzhou, China
- Present affiliation: Department of Medical Oncology; Guangzhou First People’s Hospital; Guangzhou Medical University; Guangzhou, China
| | - Max S Wicha
- Comprehensive Cancer Center; University of Michigan; Ann Arbor, MI USA
| | - Alfred E Chang
- Comprehensive Cancer Center; University of Michigan; Ann Arbor, MI USA
| | - Jian-chuan Xia
- State Key Laboratory of Oncology in Southern China and Department of Experimental Research; Sun Yat-sen University Cancer Center; Guangzhou, China
| | - Xiubao Ren
- Department of Biotherapy; Tianjin University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Immunology and Biotherapy; Tianjin, China
| | - Qiao Li
- Comprehensive Cancer Center; University of Michigan; Ann Arbor, MI USA
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Lu Y, Wu Z, Peng Q, Ma L, Zhang X, Zhao J, Qin X, Li S. Role of IL-4 gene polymorphisms in HBV-related hepatocellular carcinoma in a Chinese population. PLoS One 2014; 9:e110061. [PMID: 25295591 PMCID: PMC4190355 DOI: 10.1371/journal.pone.0110061] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2014] [Accepted: 09/08/2014] [Indexed: 12/16/2022] Open
Abstract
Background Interleukin-4 (IL-4) is best known as an important mediator and modulator of immune and inflammatory responses. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer, and genetic variations in the IL-4 gene may be associated with the risk of hepatitis B virus (HBV)-related HCC. However, few studies have been conducted on their association. Objectives To clarify the effects of IL-4 gene polymorphisms on the risk of HBV-related HCC, two common variants, −590C/T (rs2243250) and −33C/T (rs2070874), and their relationship with HBV-related disease risk were investigated in a Chinese population. Methods IL-4 −590C/T and −33C/T polymorphisms were examined in 154 patients with HBV-related HCC, 62 patients with HBV-induced liver cirrhosis (LC), 129 patients with chronic hepatitis B (CHB), and 94 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. Results Overall, no significant differences were observed regarding the IL-4 −590C/T and −33C/T polymorphism genotypes, alleles, or haplotypes between the patient groups and the healthy controls. However, the CC genotypes of IL-4 −590C/T and −33C/T polymorphisms were observed to be significantly associated with CHB in subgroup analysis in males [CC versus TT (OR: 4.193, 95% CI: 1.094–16.071, P = 0.037; and OR: 3.438, 95% CI: 1.032–11.458, P = 0.044) and CC versus TT+CT (OR: 4.09, 95% CI: 1.08–15.49, P = 0.038; and OR: 3.43, 95% CI: 1.04–11.28, P = 0.042)]. Conclusions These findings suggest that genetic variants in IL-4 −590C/T and −33C/T polymorphisms may be a risk factor for CHB in Chinese males but not for HBV-related LC or HCC.
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Affiliation(s)
- Yu Lu
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Zhitong Wu
- Department of Clinical Laboratory, Guigang People’s Hospital, Guigang, Guangxi, China
| | - Qiliu Peng
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Liping Ma
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Xiaolian Zhang
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jiangyang Zhao
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Xue Qin
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- * E-mail: (XQ); (SL)
| | - Shan Li
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- * E-mail: (XQ); (SL)
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Vukobrat-Bijedic Z, Mehmedovic A, Redzepovic A, Gogov B. Use of serum levels of proinflammatory cytokine IL-1alpha in chronic hepatitis B. Med Arch 2014; 68:94-7. [PMID: 24937930 PMCID: PMC4272509 DOI: 10.5455/medarh.2014.68.94-97] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background: The reasons for the chronic viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. Interleukin-1 (IL-1) is a proinflammatory cytokine and some studies have demonstrated that IL-1 production was impaired in patients with chronic infections of hepatitis B virus, implying that IL-1 may play a role in viral clearance, progression of fibrosis and in malignant potential of HBV. In this study, along with routine laboratory tests, has been performed the analysis of serum levels of proinflammatory cytokine IL-1 α in order of better understanding and monitoring of chronic hepatitis B. Objective: The aim of this study was to analyze the usefulness of laboratory tests, which are routinely used in the assessment of liver disease with specified immunological parameters in patients with chronic hepatitis B. Patients and methods: Total of 60 subjects was divided into two groups: HBV- PCR positive and negative group. The control group of 30 healthy participants was included. Apart from standard laboratory tests, the analysis included serum levels of cytokine IL-1 α. Results and discussion: IL-1α had the highest mean concentration in group 1–viral hepatitis C, with PCR positive test (5.73 pg / ml), and then in group 2- viral hepatitis B, PCR negative test (5.39 pg / ml). ANOVA test proves that IL-1α in the healthy group (3) was different from other groups as follows: in relation to group 1 statistical significance level was p <0.001 (F = 32 75 5); in relation to group 2 was also statistically significant at p <0.001 (F = 182 361); Cytokine IL-1 was statistically analyzed separately and compared by group 1 and 2 using Student t-test for independent samples. Statistical significance was observed at p = 0.026. IL-1 α was positively correlated with the duration of the illness (p <0.01) and with serum ALT activity (p <0.01) and serum AST activity (p <0.01). Using multivariate analysis model “Factor Analysis”, was made significant stratification predictive parameters in relation to the cytokine IL-1α, stratified significance is indicated as follows: 1. Age, 2. history of receiving transfusions, 3. ALT, 4. AST, 5. MELD score (negative), 6. Child-Pugh score (Negative). Conclusion: IL-1α was significantly elevated in inflammatory conditions of pronounced activity (PCR positive hepatitis). IL-1α may have important role as marker of both inflammation and hepatic injury, particularly in the course of hepatitis B. Results suggest that inflammatory and immune parameters, analyzed together can significantly contribute to the understanding and predicting of chronic liver damage. IL-1 can be used as important parameter of inflammatory activity and fibrosis evaluation and eventually prediction of malignant transformation in chronic liver damage.
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Affiliation(s)
- Zora Vukobrat-Bijedic
- Department of Gastroenterology and Hepatology, Referral Centre for gastrointestinal Endoscopy, Clinical Centre, University of Sarajevo, Bosnia and Herzegovina
- Corresponding author: prof. Zora Vukobrat-Bijedic, MD, PhD. Department of Gastroenterology and Hepatology, Clinical Centre, University of Sarajevo, Sarajevo, Bolnicka 25, Bosnia and Herzegovina. E-mail:
| | - Amila Mehmedovic
- Department of Gastroenterology and Hepatology, Referral Centre for gastrointestinal Endoscopy, Clinical Centre, University of Sarajevo, Bosnia and Herzegovina
| | - Amir Redzepovic
- Institute for Emergency Medical Services, Sarajevo, Bosnia and Herzegovina
| | - Bisera Gogov
- Department of Gastroenterology and Hepatology, Referral Centre for gastrointestinal Endoscopy, Clinical Centre, University of Sarajevo, Bosnia and Herzegovina
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Lin J, Wu JF, Zhang Q, Zhang HW, Cao GW. Virus-related liver cirrhosis: molecular basis and therapeutic options. World J Gastroenterol 2014; 20:6457-69. [PMID: 24914367 PMCID: PMC4047331 DOI: 10.3748/wjg.v20.i21.6457] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 01/10/2014] [Accepted: 03/08/2014] [Indexed: 02/07/2023] Open
Abstract
Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8(+) T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.
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Moens U, Van Ghelue M, Ehlers B. Are human polyomaviruses co-factors for cancers induced by other oncoviruses? Rev Med Virol 2014; 24:343-60. [PMID: 24888895 DOI: 10.1002/rmv.1798] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Revised: 04/25/2014] [Accepted: 05/07/2014] [Indexed: 12/16/2022]
Abstract
Presently, 12 human polyomaviruses are known: BK polyomavirus (BKPyV), JCPyV, KIPyV, WUPyV, Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7, Trichodysplasia spinulosa-associated polyomavirus, HPyV9, HPyV10, STLPyV and HPyV12. In addition, the non-human primate polyomavirus simian virus 40 (SV40) seems to circulate in the human population. MCPyV was first described in 2008 and is now accepted to be an etiological factor in about 80% of the rare but aggressive skin cancer Merkel cell carcinoma. SV40, BKPyV and JCPyV or part of their genomes can transform cells, including human cells, and induce tumours in animal models. Moreover, DNA and RNA sequences and proteins of these three viruses have been discovered in tumour tissue. Despite these observations, their role in cancer remains controversial. So far, an association between cancer and the other human polyomaviruses is lacking. Because human polyomavirus DNA has been found in a broad spectrum of cell types, simultaneous dwelling with other oncogenic viruses is possible. Co-infecting human polyomaviruses may therefore act as a co-factor in the development of cancer, including those induced by other oncoviruses. Reviewing studies that report co-infection with human polyomaviruses and other tumour viruses in cancer tissue fail to detect a clear link between co-infection and cancer. Directions for future studies to elaborate on a possible auxiliary role of human polyomaviruses in cancer are suggested, and the mechanisms by which human polyomaviruses may synergize with other viruses in oncogenic transformation are discussed.
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Affiliation(s)
- Ugo Moens
- University of Tromsø, Faculty of Health Sciences, Institute of Medical Biology, Molecular Inflammation Research Group, Tromsø, Norway
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Colecchia A, Schiumerini R, Cucchetti A, Cescon M, Taddia M, Marasco G, Festi D. Prognostic factors for hepatocellular carcinoma recurrence. World J Gastroenterol 2014; 20:5935-5950. [PMID: 24876717 PMCID: PMC4033434 DOI: 10.3748/wjg.v20.i20.5935] [Citation(s) in RCA: 132] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 11/14/2013] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
The recurrence of hepatocellular carcinoma, the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide, represents an important clinical problem, since it may occur after both surgical and medical treatment. The recurrence rate involves 2 phases: an early phase and a late phase. The early phase usually occurs within 2 years after resection; it is mainly related to local invasion and intrahepatic metastases and, therefore, to the intrinsic biology of the tumor. On the other hand, the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment. Since recent studies have reported that early and late recurrences may have different risk factors, it is clinically important to recognize these factors in the individual patient as soon as possible. The aim of this review was, therefore, to identify predicting factors for the recurrence of hepatocellular carcinoma, by means of invasive and non-invasive methods, according to the different therapeutic strategies available. In particular the role of emerging techniques (e.g., transient elastography) and biological features of hepatocellular carcinoma in predicting recurrence have been discussed. In particular, invasive methods were differentiated from non-invasive ones for research purposes, taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.
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Besharat S, Katoonizadeh A, Moradi A. Potential mutations associated with occult hepatitis B virus status. HEPATITIS MONTHLY 2014; 14:e15275. [PMID: 24829588 PMCID: PMC4013497 DOI: 10.5812/hepatmon.15275] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Revised: 01/14/2014] [Accepted: 02/20/2014] [Indexed: 12/11/2022]
Abstract
CONTEXT Occult hepatitis B virus (HBV) status (OHBS) is simply defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in the serum), in the absence of serum HBV surface antigen (HBsAg). Importance of OHBS is mostly clinical, related to its possible role in spreading through blood transfusion and liver transplantation; causing classic forms of HBV. Mechanisms underlying this entity are poorly defined. Several possibilities have been suggested, with major classification into two groups: defective host immune response and viral replication activity through mutations of HBV DNA sequence. Mutations are extensively investigated in all four overlapping open reading frames (ORFs) of HBV genome, to define their possible role in the pathogenesis of OHBS. Some of these mutations like S-escape mutants could not be detected by the routine available assays, making them difficult to diagnosis. Therefore, trying to detect this covert condition could be more helpful for defining better preventive and therapeutic strategies. EVIDENCE ACQUISITION In the present study we provided an in-depth review of the most important new data available on different mutations in HBV genome of patients with OHBS, which may play a role in the pathogenesis of OHBS. The data were collected through reviewing the full-text articles, identified by the PubMed search, using the following keywords and their different combinations: occult hepatitis B, HBV genome, "a" determinant, HBV open reading frames, S mutations, X mutations, P mutations and C mutations. RESULTS Variants within the major hydrophilic region (MHR) of the HBsAg, deletions in the pre-S1region, codon stop in the S open reading frames (ORF), sporadic non common mutations, some mutations affecting the posttranslational production of HBV proteins in the S ORF like deletion mutations, mutations in start codon and nucleotide changes in the X ORF, deletion and point mutations in P ORF and sometimes, nucleotide substitution in the C ORF are among the assumed mutations detected to have a role in OHBS appearance. CONCLUSIONS Studies mostly lacked a control group and the whole-length HBV sequencing was scant with conflicting results, suggesting that OHBS is often a result of multiple mechanisms. Additional studies on full-length HBV genomes from occult and non-occult HBV cases may shed more light on the interplay between different mechanisms involved in the pathogenesis of OHBS.
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Affiliation(s)
- Sima Besharat
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, IR Iran
| | - Aezam Katoonizadeh
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Abdolvahab Moradi
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, IR Iran
- Corresponding Author: Abdolvahab Moradi, Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, IR Iran. Tel: +98-1712340835; +98-9111772107, Fax: +98-1712369210, E-mail:
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Du Y, Han X, Pu R, Xie J, Zhang Y, Cao G. Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk. Front Med 2014; 8:217-26. [PMID: 24748463 DOI: 10.1007/s11684-014-0326-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Accepted: 01/07/2014] [Indexed: 02/07/2023]
Abstract
This study was designed to investigate the contribution of miRNA-122-binding site polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis B virus (HBV) mutations in the risk of hepatocellular carcinoma (HCC). A total of 1021 healthy controls, 302 HBV surface antigen (HBsAg) seroclearance subjects, and 2011 HBsAg-positive subjects (including 1021 HCC patients) were enrolled in this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were determined by direct sequencing. Multivariate logistic regression analyses were performed to test the associations of rs3783553, mutations, and their interactions with the risk of HCC. No significant association was found between rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance subjects, HBsAg-positive subjects without HCC, and all controls. Additionally, rs3783553 was not significantly associated with chronic HBV infection, liver cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and high viral load (> 10(4) copies/ml). However, the TTCA insertion allele of rs3783553 was significantly associated with an increased frequency of HBV C7A mutation compared with homozygous TTCA deletion carriers [(del/ins + ins/ins) vs. del/del, adjusted odds ratio (OR)= 1.48, 95% confidence interval (CI)= 1.09-2.02, P = 0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 (95% CI = 0.42-0.98; P = 0.041) after age and HBV genotype were adjusted. Although rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC, its variant allele may predispose the host to selecting HBV C7A mutation during evolution and significantly reduce the risk of HCC caused by HBV preS deletion. This study provides an insight into the complex host-virus interaction in HBV-induced hepatocarcinogenesis and is helpful in determining HBsAg-positive subjects who are likely to develop HCC.
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Affiliation(s)
- Yan Du
- Department of Epidemiology, Second Military Medical University, Shanghai, 200433, China
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Mixson-Hayden T, Lee D, Ganova-Raeva L, Drobeniuc J, Stauffer WM, Teshale E, Kamili S. Hepatitis B virus and hepatitis C virus infections in United States-bound refugees from Asia and Africa. Am J Trop Med Hyg 2014; 90:1014-20. [PMID: 24732462 DOI: 10.4269/ajtmh.14-0068] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The aim of this study was to determine the prevalence of active hepatitis B and C virus infections among refugees from various countries in Africa and Asia. Pre-admission serum samples collected during 2002-2007 from refugees originating from Bhutan (N = 755), Myanmar (N = 1076), Iraq (N = 1137), Laos (N = 593), Thailand (N = 622), and Somalia (N = 707) were tested for hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA. The HBV DNA (genotypes A, B, C, and G) was detected in 12.1% of samples negative for anti-HBs. Highest HBV prevalence was found among Hmong; lowest among Bhutanese. The HCV RNA (genotypes 1a, 1b, 1c, 3b, 6n, and 6m) was detected in 1.3% of the samples. Highest HCV prevalence was found among Hmong from Thailand; lowest among Iraqis. Screening specific refugee groups at high risk for viral hepatitis infections will identify infected individuals who could benefit from referral to care and treatment and prevent further transmissions.
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Affiliation(s)
- Tonya Mixson-Hayden
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia; University of Minnesota, Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Deborah Lee
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia; University of Minnesota, Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Lilia Ganova-Raeva
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia; University of Minnesota, Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Jan Drobeniuc
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia; University of Minnesota, Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, Minnesota
| | - William M Stauffer
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia; University of Minnesota, Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Eyasu Teshale
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia; University of Minnesota, Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, Minnesota
| | - Saleem Kamili
- Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia; University of Minnesota, Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, Minnesota
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48
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Finegold MJ, López-Terrada DH. Hepatic Tumors in Childhood. PATHOLOGY OF PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2014:547-614. [DOI: 10.1007/978-3-642-54053-0_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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49
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Ghasemi R, Ghaffari SH, Momeny M, Pirouzpanah S, Yousefi M, Malehmir M, Alimoghaddam K, Ghavamzadeh A. Multitargeting and antimetastatic potentials of silibinin in human HepG-2 and PLC/PRF/5 hepatoma cells. Nutr Cancer 2013; 65:590-9. [PMID: 23659451 DOI: 10.1080/01635581.2013.770043] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common sort of primary liver malignancy with poor prognosis. This study aimed at examining the effects of silibinin (a putative antimetastatic agent) on some transcriptional markers mechanistically related to HCC recurrence and metastasis in HepG-2 [hepatitis B virus (HBV)-negative and P53 intact) and PLC/PRF/5 (HBV-positive and P53 mutated) cells. The expression of 27 genes in response to silibinin was evaluated by real-time RT-PCR. The MMP gelatinolytic assay and microculture tetrazolium test (MTT) were tested. Silibinin was capable of suppressing the transcriptional levels of ANGPT2, ATP6L, CAP2, CCR6, CCR7, CLDN-10, cortactin, CXCR4, GLI2, HK2, ID1, KIAA0101, mortalin, PAK1, RHOA, SPINK1, and STMN1 as well as the enzymatic activity of MMP-2 but promoted the transcripts of CREB3L3, DDX3X, and PROX1 in both cells. Some significant differences between the cells in response to silibinin were detected that might be related to the differences of the cells in terms of HBV infection and/or P53 mutation, suggesting the possible influence of silibinin on HCC through biological functions of these 2 prognostic factors. In conclusion, our findings suggest that silibinin could potentially function as a multitargeting antimetastatic agent and might provide new insights for HCC therapy particularly for HBV-related and/or P53-mutated HCCs.
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Affiliation(s)
- Reza Ghasemi
- Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
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50
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Lu T, Seto WK, Zhu RX, Lai CL, Yuen MF. Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection. World J Gastroenterol 2013; 19:8887-8894. [PMID: 24379612 PMCID: PMC3870540 DOI: 10.3748/wjg.v19.i47.8887] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 10/26/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with the majority of cases associated with persistent infection from hepatitis B virus (HBV) or hepatitis C virus (HCV). Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV infection. High-risk infected individuals can now be identified by the usage of risk predictive scores. Vaccination plays a central role in the prevention of HBV-related HCC. Treatment of chronic HBV infection, especially by nucleoside analogue therapy, could also reduce the risk of HBV-related HCC. Concerning HCV infection, besides the advocation of universal precautions to reduce the rate of infection, pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic response. Recently there has been mounting evidence on the role of chemopreventive agents in reducing HBV- and HCV-related HCC. The continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.
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