scholarly journals Activated TAZ Induces Liver Cancer in Collaboration with EGFR/HER2 Signaling Pathways

2021 ◽  
Author(s):  
Hyuk Moon ◽  
Hye Jin Choi ◽  
Do Young Kim ◽  
Simon Weonsang Ro
Keyword(s):  
Liver Cancer ◽  
Signaling Pathways ◽  
Primary Liver Cancer ◽  
Active Form ◽  
Health Concern ◽  
Liver Carcinogenesis ◽  
Regulator Protein ◽  
Incidence And Mortality ◽  
Her2 Signaling ◽  
Immunohistochemical Analyses

Abstract Liver cancer is a major global health concern due to the steady increases in its incidence and mortality. Transcription factors, yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ)have emerged as critical regulators in human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), the two major types of primary liver cancer. However, our study as well as other previous reports have shown that activation of YAP and TAZ (YAP/TAZ) in adult murine livers is insufficient for the development of liver cancer, suggesting a requirement for an additional oncogenic collaborator for liver carcinogenesis in adulthood. Therefore,we sought to identifythe oncogenic partners of YAP/TAZ that promote hepatocarcinogenesis in adults. Through database analyses, we identified EGFR/HER2signaling to be essential in human cancerswith high TAZ activity.Furthermore,immunohistochemical analyses showedthat human HCC and CC tissues with high YAP/TAZ activities exhibited concomitant activation of EGFR/HER2downstream signaling pathways. To demonstrate that EGFR/HER2 signaling promotes YAP/TAZ-mediated hepatocarcinogenesis, a constitutively active form of TAZ was simultaneously expressed in murine adult livers with effector molecules downstream of EGFR/HER2 signaling pathways.Interestingly, activated TAZ and BRAFinduced HCC, whereas activated TAZ and PI3K led to the development of CC-like cancer, demonstrating that TAZ collaborates with EGFR/HER2 signaling pathways to induce both HCC and CC.

scholarly journals Systematic Elucidation of the Potential Mechanisms of Core Chinese Materia Medicas in Treating Liver Cancer Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhulin Wu ◽  
Lina Yang ◽  
Li He ◽  
Lianan Wang ◽  
Lisheng Peng
Keyword(s):  
Data Mining ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Target Genes ◽  
Primary Liver Cancer ◽  
Network Pharmacology ◽  
Data Mining Technique ◽  
Antitumor Effects ◽  
Bioactive Ingredients ◽  
Common Target

Objective. In this study, the data mining method was used to screen the core Chinese materia medicas (CCMMs) against primary liver cancer (PLC), and the potential mechanisms of CCMMs in treating PLC were analyzed based on network pharmacology. Methods. Traditional Chinese medicine (TCM) prescriptions for treating PLC were obtained from a famous TCM doctor in Shenzhen, China. According to the data mining technique, the TCM Inheritance Support System (TCMISS) was applied to excavate the CCMMs in the prescriptions. Then, bioactive ingredients and corresponding targets of CCMMs were collected using three different TCM online databases, and target genes of PLC were obtained from GeneCards and OMIM. Afterwards, common targets of CCMMs and PLC were screened. Furthermore, a network of CCMMs bioactive ingredients and common target gene was constructed by Cytoscape 3.7.1, and gene ontology (GO) and signaling pathways analyses were performed to explain the mechanism of CCMMs in treating PLC. Besides, protein-protein interaction (PPI) analysis was used to identify key target genes of CCMMs, and the prognostic value of key target genes was verified using survival analysis. Results. A total of 15 high-frequency Chinese materia medica combinations were found, and CCMMs (including Paeoniae Radix Alba, Radix Bupleuri, Macrocephalae Rhizoma, Coicis Semen, Poria, and Curcumae Radix) were identified by TCMISS. A total of 40 bioactive ingredients (e.g., quercetin, kaempferol, and naringenin) of CCMMs were obtained, and 202 common target genes of CCMMs and PLC were screened. GO analysis indicated that biological processes of CCMMs were mainly involved in response to drug, response to ethanol, etc. Pathway analysis demonstrated that CCMMs exerted its antitumor effects by acting on multiple signaling pathways, including PI3K-Akt, TNF, and MAPK pathways. Also, some key target genes of CCMMs were determined by PPI analysis, and four genes (MAPK3, VEGFA, EGF, and EGFR) were found to be correlated with survival in PLC patients. Conclusion. Based on data mining and network pharmacology methods, our results showed that the therapeutic effect of CCMMs on PLC may be realized by acting on multitargets and multipathways related to the occurrence and development of PLC.

scholarly journals Improved Trends in the Mortality-To-Incidence Ratios for Liver Cancer in Countries With High Development Index and Health Expenditures

2021 ◽  
Author(s):  
Chi-Chih Wang ◽  
Hsin-Hung Chen ◽  
Wen-Wei Sung ◽  
Ming-Chang Tsai
Keyword(s):  
Liver Cancer ◽  
Health Expenditure ◽  
Primary Liver Cancer ◽  
World Health ◽  
Aging Effects ◽  
Development Index ◽  
Current Health ◽  
Incidence And Mortality ◽  
The World ◽  
Per Capita

Abstract Primary liver cancer is one of leading causes of death globally. Liver cancer has the uniqueness of geographical distribution as it predisposes viral infection etiologies and aging effects. We speculate if the human development index (HDI), current health expenditure (CHE) per capita, and current health expenditure on gross domestic product (CHE/GDP) can affect the incidence numbers, mortality numbers, or mortality-to-incidence ratios (MIRs) of liver cancer worldwide. Data was obtained from GLOBOCAN health data and statistics from the World Health Organization. MIRs and the changes in MIR over time (𝛿MIR) were used to evaluate the correlation of expenditures on healthcare and the HDI disparities via Spearman's rank correlation coefficient. The incidence and mortality of crude rate have significant associations with HDI, CHE per capita, and CHE/GDP. Specifically, there were significant associations between 𝛿MIR and HDI as well as between 𝛿MIR and CHE per capita. However, there were no significant associations between 𝛿MIR and CHE/GDP. We evidenced that favorable liver cancer 𝛿MIR was not associated with CHE/GDP, although it had significant association with HDI and CHE per capita. This result is worthy of the attention of the public health system all over the world.

scholarly journals Trends in Incidence and Mortality of Primary Liver Cancer in Lithuania 1998–2015

2021 ◽  
Vol 18 (3) ◽  
pp. 1191
Author(s):  
Audrius Dulskas ◽  
Povilas Kavaliauskas ◽  
Kestutis Zagminas ◽  
Ligita Jancoriene ◽  
Giedre Smailyte
Keyword(s):  
Liver Cancer ◽  
Cancer Incidence ◽  
Ductal Carcinoma ◽  
Primary Liver Cancer ◽  
Age Groups ◽  
Developed Countries ◽  
Mortality Rates ◽  
Incidence Rates ◽  
Incidence And Mortality ◽  
Cancer Incidence Rates

Background: Recently, reports have suggested that rates of liver cancer have increased during the last decades in developed countries; increasing hepatocellular carcinoma and cholangiocarcinoma rates were reported. The aim of this study was to examine time trends in incidence and mortality rates of liver cancer for the period of 1998–2015 in Lithuania by sex, age, and histology. Methods: We examined the incidence of liver cancer from 1998 to 2015 using data from the Lithuanian Cancer Registry. Age-standardized incidence rates were calculated by sex, age, and histology. Trends were analyzed using the Joinpoint Regression Program to estimate the annual percent change. Results: A total of 3086 primary liver cancer cases were diagnosed, and 2923 patients died from liver cancer. The total number of liver cancer cases changed from 132 in 1998 to 239 in 2015. Liver cancer incidence rates changed during the study period from 5.02/100,000 in 1998 to 10.54/100,000 in 2015 in men and from 2.43/100,000 in 1998 to 6.25/100,000 in 2015 in women. Annual percentage changes (APCs) in the age-standardized rates over this period were 4.5% for incidence and 3.6% for mortality. Hepatocellular cancer incidence rates were stable from 1998 to 2005 (APC −5.9, p = 0.1) and later increased by 6.7% per year (p < 0.001). Intrahepatic ductal carcinoma incidence increased by 8.9% per year throughout the study period. The rise in incidence was observed in all age groups; however, in age groups < 50 and between 70 and 79 years, observed changes were not statistically significant. For mortality, the significant point of trend change was detected in 2001, where after stable mortality, rates started to increase by 2.4% per year. Conclusions: Primary liver cancer incidence and mortality increased in both sexes in Lithuania. The rise om incidence was observed in both sexes and main histology groups. The increasing incidence trend may be related to the prevalence of main risk factors (alcohol consumption, hepatitis B and C infections. and diabetes).

scholarly journals Descriptive epidemiology of incidence and mortality of primary liver cancer in 185 countries: evidence from GLOBOCAN 2018

2020 ◽  
Vol 50 (12) ◽  
pp. 1370-1379
Author(s):  
Rajesh Sharma
Keyword(s):  
Mortality Rate ◽  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Descriptive Epidemiology ◽  
Hepatitis C Infection ◽  
Obesity Control ◽  
Incidence And Mortality ◽  
Global Age ◽  
Standardized Mortality Rate ◽  
Screening Approaches

Abstract Purpose This study aims to examine the burden of primary liver cancer in 185 countries in 2018. Methods The estimates of incidence, mortality and prevalence of primary liver cancer were procured from GLOBOCAN 2018. The development status of a country was measured using the human development index—a composite indicator of income per capita, education and life expectancy. Results Globally, primary liver cancer resulted in an estimated 781 631 deaths at age-standardized mortality rate of 8.5/100 000, and 841 080 cases were estimated to be diagnosed in 2018. Males accounted for 596 574 cases and 548 375 deaths, which is more than twice the burden of primary liver cancer in females (cases: 244 506; deaths: 233 456). The global age-standardized incidence rate was 9.3/100 000 in 2018, varying from Morocco (1.1/100 000) to Mongolia (93.7/100 000). There were remarkable variations in terms of age-standardized mortality rate, too, which ranged from 1/100 000 in Nepal to 75.4/100 000 in Mongolia. East Asia was the top region contributing 55.6% of global cases and 54.7% of global deaths. Conclusions Since majority of the primary liver cancer burden pertains to hepatocellular carcinoma and screening approaches are yet to be fully proven, the policy focus must be on prevention approaches through the hepatitis-B vaccine, early detection of hepatitis-C infection, reduced alcohol consumption, obesity control, reduced aflatoxin exposure and containment of other modifiable risk factors.

scholarly journals Emerging Regulatory Mechanisms Involved in Liver Cancer Stem Cell Properties in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Duoduo Lv ◽  
Liyu Chen ◽  
Lingyao Du ◽  
Lingyun Zhou ◽  
Hong Tang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Primary Liver Cancer ◽  
Treatment Resistance ◽  
Current Evidence ◽  
New Developments ◽  
Regulatory Pathways ◽  
Liver Cancer Stem Cell ◽  
Improve Patient

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and one of the leading causes of cancer-related deaths worldwide. A growing body of evidence supports the hypothesis that HCC is driven by a population of cells called liver cancer stem cells (LCSCs). LCSCs have been proposed to contribute to malignant HCC progression, including promoting tumor occurrence and growth, mediating tumor metastasis, and treatment resistance, but the regulatory mechanism of LCSCs in HCC remains unclear. Understanding the signaling pathways responsible for LCSC maintenance and survival may provide opportunities to improve patient outcomes. Here, we review the current literature about the origin of LCSCs and the niche composition, describe the current evidence of signaling pathways that mediate LCSC stemness, then highlight several mechanisms that modulate LCSC properties in HCC progression, and finally, summarize the new developments in therapeutic strategies targeting LCSCs markers and regulatory pathways.

Molecular epidemiology of liver cancer: Liver cancer incidence and mortality pattern worldwide

2021 ◽  
Vol 1 (1) ◽  
pp. 018-023
Author(s):  
Nasrin Jafari ◽  
Roya Dolatkhah
Keyword(s):  
High Risk ◽  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Incidence Rates ◽  
Screening Tests ◽  
Average Risk ◽  
Mortality Pattern ◽  
Cancer Pathogenesis ◽  
Incidence And Mortality ◽  
Liver Cancers

Primary liver cancer was the sixth most prevalent cancer and third leading cause of cancer mortality worldwide. The highest rates of incidence and mortality were reported in Eastern Asia and it was 2 to 3 times more common than females in most regions. The summary estimates of the global trends in incidence rates of liver cancer indicated decreasing trends in many Asian high-risk countries, however increasing trends for North American and European countries. Understanding the several involved cells signaling pathways in liver cancer pathogenesis provide an opportunity to identify novel targets that can be utilized for therapeutic and diagnostic modalities. At this time there are only a few effective strategies to prevent or treat liver cancer, and, therefore, a great deal of research is being conducted on liver cancer early detection and prevention. There are no widely recommended screening tests for liver cancer in people who are at average risk at this time. But, testing might be recommended for some people at higher risk. However researchers are studying ways to prevent or treat hepatitis infections before they cause liver cancers. Research into developing a vaccine to prevent hepatitis C is ongoing. Since population-based methods for screening the disease have not been introduced, the greatest focus should be placed on the predominant risk factors for the disease in older men, further studies should be conducted and high-risk provinces should be spotlighted.

scholarly journals The Burden and Trends of Primary Liver Cancer Caused by Specific Etiologies from 1990 to 2017 at the Global, Regional, National, Age, and Sex Level Results from the Global Burden of Disease Study 2017

Liver Cancer ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 563-582 ◽  
Author(s):  
Longfei Lin ◽  
Lei Yan ◽  
Yuling Liu ◽  
Changhai Qu ◽  
Jian Ni ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Incidence ◽  
Burden Of Disease ◽  
Primary Liver Cancer ◽  
Global Burden Of Disease ◽  
Global Burden ◽  
Targeted Prevention ◽  
Cancer Burden ◽  
Incidence And Mortality ◽  
Disease Study

Background: Liver cancer is one of the leading causes of cancer-related deaths worldwide. The primary causes of liver cancer include hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol consumption, nonalcoholic fatty liver disease, and other factors. Aims: The objective of this study was to evaluate the global and sex-, age-, region-, country-, and etiology-related liver cancer burden, as well as the trends in liver cancer caused by different etiologies. Methods: The causes of liver cancer from 1990 to 2017, including global, regional, and national liver cancer incidence, mortality, and etiology, were collected from the Global Burden of Disease study 2017, and the time-dependent change in the trends of liver cancer burden was evaluated by annual percentage change. Results: The global liver cancer incidence and mortality have been increasing. There were 950,000 newly-diagnosed liver cancer cases and over 800,000 deaths in 2017, which is more than twice the numbers recorded in 1990. HBV and HCV are the major causes of liver cancer. HBV is the major risk factor of liver cancer in Asia, while HCV and alcohol abuse are the major risk factors in the high sociodemographic index and high human development index regions. The mean onset age and incidence of liver cancer with different etiologies have gradually increased in the past 30 years. Conclusions: The global incidence is still rising and the causes have national, regional, or population specificities. More targeted prevention strategies must be developed for the different etiologic types in order to reduce liver cancer burden.

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