Viral and host inflammation-related factors that can predict the prognosis of hepatocellular carcinoma

Chen, Liping; Zhang, Qi; Chang, Wenjun; Du, Yan; Zhang, Hongwei; Cao, Guangwen

doi:10.1016/j.ejca.2012.01.015

Cited by 100 publications

(84 citation statements)

References 123 publications

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“…In inflammatory microenvironment, inflammatory mediators such as prostaglandin E2, leukotrienes, cytokines, and chemokinesare highly induced via autocrine or paracrine modes of action [102] , resulting in abnormal transformation of the tissue microenvironment, infiltration of dysfunctional immune cells, and decreased epithelial integrity, thus promoting cancer evolution. Non-resolving inflammation not only promote the occurrence of cancers of the most histotypes, but also facilitate distant metastasis and the recurrence after the treatment [46,103,104] , indicating that non-resolving inflammation promotes the development of cancers in the entire course of cancer evolution.…”

Section: Key Issues Regarding Cancer Evo-dev Indispensable Role Of Nomentioning

confidence: 99%

“…The species and frequencies of certain HBV mutations in adjacent tissues are different in HBV-infected patients with HCC (HBV-HCC patients) with distinct postoperative prognosis. Together with immune markers and expression levels of inflammatory genes in adjacent hepatic tissues, the HBV mutations can be applied to predict postoperative prognosis in HCC patients [46] . The HBV mutations in the EnhII/BCP/PreC region such as A1762T/G1764A in the remnant liver after curative surgery or in the circulation before liver transplantation have been proven to be predictive markers for postoperative survival and HCC recurrence, although this result has not been repeated by some research groups [47][48][49] .…”

Section: Reduction Of Cd8mentioning

confidence: 99%

“…Although surgical technologies for the treatment of liver cancer have been improved, postoperative prognosis remains to be precisely evaluated [5][6][7] . Active inflammation on chronic inflammation background, as reflected by an Ishak hepatic inflammation score (> 6), a higher neutrophil-tolymphocyte ratio (> 5), and a higher C-reactive protein in sera (> 0.3 mg/dL), etc., also indicate a poor postoperative prognosis such as postoperative recurrence and shorter recurrence-free survival in HBV-related HCC (HBV-HCC) patients [8,9] . Nuclear factor-κB (NF-κB) and signal transducers and activators of transcription 3 (STAT3) are two most important transcription factors involved in inflammatory pathways that play predominant roles in carcinogenesis, especially in HBV-induced hepatocarcinogenesis [10,11] .…”

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confidence: 99%

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Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

Cao¹

2017

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How to cite this article: Cao GW. Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis. Hepatoma Res 2017;3:241-59.Non-resolving inflammation, which may be maintained by infection, pollution, and metabolic stimulants and their interactions with immunogenetic predisposition, provides a fertile field for cancer development. This is strongly evident in hepatocellular carcinoma. Here, the framework of a hypothesis called Cancer Evo-Dev is presented, based on the advances in hepatitis B virusinduced hepatocarcinogenesis. Several aspects central to this theory are as follows: (1) immune imbalance caused by the interaction of immunogenetic predispositions and hepatitis B virus infection maintains non-resolving inflammation; (2) active inflammation executants promote mutations in viral and host genomes via disbalancing mutagenic forces including cytidine deaminases and mutation-repairing forces including uracil-DNA glycosylases, thus promoting cancer-related somatic mutations and viral mutations; (3) a small percentage of the cells whose somatic mutations alter the survival signalling adapt to the inflammatory microenvironment, de-differentiate via demethylating role of cytidine deaminases, and reversely develop into tumor-initiating cells (TICs); (4) under the cultivation of some factors like POSTN from tumorinfiltrating fibroblasts and M2 macrophages, TICs acquire the stemness, cancer-stem cells obtain distinct metastatic and drug-resistant potentials under the selection pressure from distinct microenvironments; (5) glycolysis persistence in the presence of oxygen provides essential energy for cell survival and the raw material for DNA synthesis. Thus, cancer development is characterized by an evolutionary process of "mutation-selection-adaptation". The framework of Cancer Evo-Dev can be verified in other cancers. Cancer Evo-Dev lays theoretical foundation for understanding the mechanisms by which inflammation promotes cancer development, and it also plays a role in specific prophylaxis, prediction, and targeted treatment of cancers. Key words:Inflammation, hepatitis B virus, mutations, hepatoma, Cancer Evo-Dev ABSTRACTArticle history:

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Section: Key Issues Regarding Cancer Evo-dev Indispensable Role Of Nomentioning

confidence: 99%

Section: Reduction Of Cd8mentioning

confidence: 99%

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confidence: 99%

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Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

Cao¹

2017

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“…One of the major contributing factors for HCC development, recurrence and metastasis is the imbalance of inflammatory response (13)(14)(15). Several indicators of systemic inflammation, such as C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio (PLR) and modified Glasgow prognostic score have been used for evaluation of inflammatory status.…”

Section: Abstract Background: a Lower Neutrophil-to-lymphocyte Ratiomentioning

confidence: 99%

Clinical Predictors for Neutrophil–to–Lymphocyte Ratio Changes in Patients with Chronic Hepatitis B Receiving Peginterferon Treatment

Liang

Chang

et al. 2017

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Abstract. Background: A lower neutrophil-to-lymphocyte ratio (NLR) was found to be associated with better clinical outcomes in hepatitis B (adjusted p=0.028, 0.005, and 0.028, respectivelyHepatitis B virus (HBV) infection is a global public health issue. There are about 250 million HBV carriers in the world, of whom roughly 600,000 die annually from HBVrelated liver disease, including liver cirrhosis and hepatocellular carcinoma (HCC) (1-4). Interferon and nucleos(t)ide analogs are two major classes of antiviral therapies against HBV. Both are capable of reducing the incidence of HCC (5-8). In view of HCC prevention, peginterferon remains superior to nucleos(t)ide analogs (9). One possible reason for this is the emergence of HBV surface antigen truncation mutations, which had increased oncogenic potentials, in patients receiving long-term nucleos(t)ide analogue therapy (9-11) and the other is the immunomodulatory properties of peginterferon, which is believed to exert anticancer effect (12).One of the major contributing factors for HCC development, recurrence and metastasis is the imbalance of inflammatory response (13-15). Several indicators of systemic inflammation, such as C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio (PLR) and modified Glasgow prognostic score have been used for evaluation of inflammatory status. Neutrophils and lymphocytes are the essential components of the tumor-related stroma, and are closely correlated to local inflammation and immune responses (16). Because blood neutrophil and lymphocyte counts are routinely checked during clinical practice, NLR is widely used as a reference for immunological status of the patients (17). Nowadays, a higher NLR has been correlated with poorer prognosis in several malignancies (18-23), including resectable and advanced . In this way, lower NLR seems to imply a lower risk and better outcome of HCC in chronic HBV-infected patients. We, therefore, hypothesized that the NLR change post peginterferon treatment might provide an explanation for its superior HCCprevention effect. Searching the literature, there is no study focusing on the change of NLR after peginterferon treatment in chronic hepatitis B patients. In this study, we aimed to clarify this important issue. 723

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“…Although tumour-adjacent tissues are pathologically categorized as "normal," they typically contain precancerous lesions and have already entered the middle stage of the cancer evolution process. The hccs that relapse more than 2 years after resection are considered to be recurrent hcc and are not a result of the initial hcc cell diffusion into remnant liver tissue 21 .…”

Section: "Dead-end" Evolution Of Hbvmentioning

confidence: 99%

Cancer Evolution–Development: Experience of Hepatitis B Virus–Induced Hepatocarcinogenesis

Liu¹,

Wu²,

Du³

et al. 2016

Current Oncology

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Here, we present the basic concept and theoretical framework of a scientific hypothesis called Cancer EvolutionDevelopment ("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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Viral and host inflammation-related factors that can predict the prognosis of hepatocellular carcinoma

Cited by 100 publications

References 123 publications

Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

Clinical Predictors for Neutrophil–to–Lymphocyte Ratio Changes in Patients with Chronic Hepatitis B Receiving Peginterferon Treatment

Cancer Evolution–Development: Experience of Hepatitis B Virus–Induced Hepatocarcinogenesis

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