Role of Virus-Related Chronic Inflammation and Mechanisms of Cancer Immune-Suppression in Pathogenesis and Progression of Hepatocellular Carcinoma

Borgia, Melissa; Bo, Michele Dal; Toffoli, Giuseppe

doi:10.3390/cancers13174387

Cited by 16 publications

(17 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HCC is the most common primary liver cancer and the second leading cause of cancer-related mortality worldwide [ 1 ]. Human HCC is an inflammation-induced cancer, and its primary causes are HBV, HCV, alcoholic steatohepatitis, and NASH [ 2 , 3 ]. Chronic viral hepatitis, alcohol abuse, and metabolic liver diseases cause chronic inflammation, which leads to continuous cycles of hepatocytes destruction and regeneration, and during compensatory hepatic regeneration, genetic abnormalities accumulate and contribute to the pathogenesis and progression of HCC [ 3 , 7 , 8 , 9 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Human HCC is an inflammation-induced cancer, and its primary causes are HBV, HCV, alcoholic steatohepatitis, and NASH [ 2 , 3 ]. Chronic viral hepatitis, alcohol abuse, and metabolic liver diseases cause chronic inflammation, which leads to continuous cycles of hepatocytes destruction and regeneration, and during compensatory hepatic regeneration, genetic abnormalities accumulate and contribute to the pathogenesis and progression of HCC [ 3 , 7 , 8 , 9 , 10 ]. The Wnt/β-catenin signaling pathway is considered an attractive candidate mediator of chronic inflammation and a critical player in HCC progression [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second leading cause of cancer-related death worldwide [ 1 ]. Hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic steatohepatitis, and non-alcoholic steatohepatitis (NASH) are the major causative factors of HCC development [ 2 , 3 ]. In most cases, HCC develops in chronic liver disease that provides the basis for premalignant lesions such as dysplastic foci and dysplastic nodules through multistep hepatocarcinogenesis [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Chronic inflammation caused by chronic viral hepatitis, alcohol abuse, and metabolic liver disease underlies the pathogenesis of HCC and leads to a continuous process of immune-mediated destruction and compensatory regeneration [ 3 , 7 , 8 ]. During this process, genetic abnormalities accumulate, and these contribute to cancer initiation and progression [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Parafibromin Is Highly Expressed in Hepatocellular Carcinoma and Its Expression Correlates with Poor Prognosis

Kim

2022

JCM

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Much progress has been made regarding the understanding of hepatocarcinogenesis, yet the long-term survival rate of HCC patients remains poor. Recent efforts have shown parafibromin has a pathologic role in many human cancers, but little is known about the effects of parafibromin in HCC. This study aimed to investigate the pattern of parafibromin expression and its clinicopathologic significance in human HCC. Immunohistochemical analysis of HCC and matched non-tumor liver tissues from 50 HCC patients showed that the nuclear expression of parafibromin was higher in HCC tissues (50/50 cases) than in non-tumor liver tissues (17/50 cases). Moreover, elevated parafibromin expression was found to be significantly correlated with the presence of microvascular invasion (p = 0.017), hepatitis virus infection-induced occurrence (p = 0.005), and poorer tumor differentiation (Edmondson–Steiner grade; p = 0.000). Kaplan–Meier analysis showed that HCC patients with elevated parafibromin expression had poorer recurrence-free (p = 0.014, log-rank test = 6.079) and overall survival (p = 0.036, log-rank test = 4.414). These findings indicate parafibromin may be related to the pathogenesis of HCC and a potential prognostic marker for HCC patients after hepatectomy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Parafibromin Is Highly Expressed in Hepatocellular Carcinoma and Its Expression Correlates with Poor Prognosis

Kim

2022

JCM

View full text Add to dashboard Cite

show abstract

“…Tumor heterogeneities, including microenvironmental discrepancies and morphological heterogeneity, are frequently reported in HCC and play a major role in tumor progression and resistance to treatment. ( Li and Wang, 2016 ), ( Borgia et al, 2021 ), ( Atwa et al, 2021 )…”

Section: Introductionmentioning

confidence: 99%

Identification of HCC Subtypes With Different Prognosis and Metabolic Patterns Based on Mitophagy

Wang

Wang²,

Sun

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Background: Mitophagy is correlated with tumor initiation and development of malignancy. However, HCC heterogeneity with reference to mitophagy has yet not been systematically explored.Materials and Methods: Mitophagy-related, glycolysis-related, and cholesterol biosynthesis-related gene sets were obtained from the Reactome database. Mitophagy-related and metabolism-related subtypes were identified using the ConsensusClusterPlus algorithm. Univariate Cox regression was analysis was performed to identify prognosis-related mitophagy regulators. Principal component analysis (PCA) was used to create composite measures of the prognosis-related mitophagy regulators (mitophagyscore). Individuals with a mitophagyscore higher or lower than the median value were classified in high- or low-risk groups. Kaplan-Meier survival and ROC curve analyses were utilized to evaluate the prognostic value of the mitophagyscore. The nomogram and calibration curves were plotted using the“rms” R package. The package “limma” was used for differential gene expression analysis. Differentially expressed genes (DEGs) between high- and low-risk groups were used as queries in the CMap database. R package “pRRophetic” and Genomics of Drug Sensitivity in Cancer (GDSC) database were used to determine the sensitivity of 21 previously reported anti-HCC drugs.Results: Three distinct HCC subtypes with different mitophagic accumulation (low, high, and intermediate mitophagy subtypes) were identified. High mitophagy subtype had the worst outcome and highest glycolysis level. The lowest degree of hypoxia and highest cholesterol biosynthesis was observed in the low mitophagy subtype; oncogenic dedifferentiation level in the intermediate mitophagy subtype was the lowest. Mitophagyscore could serve as a novel prognostic indicator for HCC.High-risk patients had a poorer prognosis (log-rank test, p < 0.001). The area under the ROC curve for mitophagyscore in 1-year survival was 0.77 in the TCGA cohort and 0.75 in the ICGC cohort. Nine candidate small molecules which were potential drugs for HCC treatment were identified from the CMap database. A decline in the sensitivity towards 21 anti-HCC drugs was observed in low-risk patients by GDSC database. We also identified a novel key gene, SPP1, which was highly associated with different mitophagic subtypes.Conclusion: Based on bioinformatic analyses, we systematically examined the HCC heterogeneity with reference to mitophagy and observed three distinct HCC subtypes having different prognoses and metabolic patterns.

show abstract

Mechanisms and network pharmacological analysis of Yangyin Fuzheng Jiedu prescription in the treatment of hepatocellular carcinoma

et al. 2022

View full text Add to dashboard Cite

Objective To identify the key drugs of Yangyin Fuzheng Jiedu prescription (YFJP) and investigate their therapeutic effects against hepatocellular carcinoma (HCC) and the potential mechanism using network pharmacology. Methods The H22 tumor‐bearing mouse model was established. Thirty male BALB/c mice were divided randomly into five groups. The mice were orally treated with either disassembled prescriptions of YFJP or saline solution continuously for 14 days. The mice were weighed every 2 days during treatment and the appearance of tumors was observed by photographing. The tumor inhibition rate and the spleen and thymus indexes were calculated. Hematoxylin and eosin and immunohistochemical staining were performed to observe the histological changes and tumor‐infiltrating lymphocytes. Cell apoptosis was determined by terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining. The proportion of CD8 + T cells and the expression of programmed cell death protein 1 (PD‐1), T cell immunoglobulin domain and mucin domain‐3 (Tim‐3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were analyzed using flow cytometry. The production of serum cytokines was detected using the Milliplex® MAP mouse high sensitivity T cell panel kit. The active components of the key drugs and HCC‐related target proteins were obtained from the corresponding databases. The putative targets for HCC treatment were screened by target mapping, and potential active components were screened by constructing a component‐target network. The interactive targets of putative targets were obtained from the STRING database to construct the protein–protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were performed based on potential targets. The gene–gene inner and component‐target‐pathway networks were constructed and analyzed to screen the key targets. Western blotting was used to evaluate the protein expression of the key targets in the tumor‐bearing mouse model. The binding activity of the key targets and compounds was verified by molecular docking. Results Among the three disassembled prescriptions of YFJP, the Fuzheng prescription (FZP) showed significant antitumor effects and inhibited weight loss during the treatment of H22 tumor‐bearing mice. FZP increased the immune organ index and the levels of CD8 + and CD3 + T cells in the spleen and peripheral blood of H22 tumor‐bearing mice. FZP also reduced the expression of PD‐1, TIGIT, and TIM3 in CD8 + T cells and the production of IL‐10, IL‐4, IL‐6, and IL‐1β. Network pharmacology and experimental validation showed that the key targets of FZP in the treatment of HCC were PIK3CA, TP53, MAPK1, MAPK3, and EGFR. The therapeutic effect on HCC was evaluated based on HCC‐related signaling pathways, including the PIK3‐Akt ...

show abstract

Role of Virus-Related Chronic Inflammation and Mechanisms of Cancer Immune-Suppression in Pathogenesis and Progression of Hepatocellular Carcinoma

Cited by 16 publications

References 152 publications

Parafibromin Is Highly Expressed in Hepatocellular Carcinoma and Its Expression Correlates with Poor Prognosis

Parafibromin Is Highly Expressed in Hepatocellular Carcinoma and Its Expression Correlates with Poor Prognosis

Identification of HCC Subtypes With Different Prognosis and Metabolic Patterns Based on Mitophagy

Mechanisms and network pharmacological analysis of Yangyin Fuzheng Jiedu prescription in the treatment of hepatocellular carcinoma

Contact Info

Product

Resources

About