The Immunology of Hepatocellular Carcinoma

Lawal, Gbemisola; Xiao, Yao; Rahnemai‐Azar, Amir A.; Tsilimigras, Diamantis I.; Bakopoulos, Anargyros; Pawlik, Timothy M.

doi:10.3390/vaccines9101184

Cited by 51 publications

(37 citation statements)

References 101 publications

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“…However, the persistence of inflammation, sustained cell death, compensatory proliferation, activation of nonparenchymal cells, and an altered immune response can promote liver fibrosis and, in turn, lead to tumorigenesis [ 6 – 8 ]. Along with the occurrence of tumors, inflammatory signals, cellular stress, epigenetic modifications [ 9 ], mitochondrial stress signaling [ 10 ], and the immune system may change [ 11 ], thus posing significant challenges to the treatment and prognosis evaluation of HCC.…”

Section: Introductionmentioning

confidence: 99%

A New Inflammation-Related Risk Model for Predicting Hepatocellular Carcinoma Prognosis

Xing

2022

BioMed Research International

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Background. Hepatocellular carcinoma (HCC) is characterized by a poor prognosis. Inflammation has a vital role in the formation and development of HCC. However, the prediction of HCC prognosis using inflammation-related genes (IRGs) remains elusive. In this study, we constructed a new IRG risk model to predict the HCC prognosis. Results. HCC-related RNA expression profiles and their corresponding clinical data were downloaded from TCGA and ICGC databases to explore the IRGs’ predicting ability. Seven hundred thirty-seven IRGs from GeneCards were used as candidate genes to construct the model. The associations of overall survival (OS) with IRGs were evaluated using the log-rank test and univariate Cox analysis, and 32 out of 737 IRGs showed predicting the potential for HCC prognosis. These IRGs were further analyzed using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses. Finally, 6 IRGs were included in an IRG risk model. Based on the cut-off of the risk score calculated according to the IRG risk model, HCC samples were divided into the high-risk and the low-risk groups. The OS of patients was lower in the high-risk group than in the low-risk group ( P < 0.05 ). The area under the receiver operating characteristic curve (AUC) of the risk score was 0.78 for 3-year survival. Univariate Cox and multivariate Cox analyses revealed that the risk score was an independent risk factor for HCC prognosis. The KEGG and GO enrichment analysis results further showed that the risk scores were closely related to inflammatory and immune pathways. In addition, the ssGSEA demonstrated that several immune cells and some immune-related pathways were negatively correlated with the risk score. Conclusions. The new IRG risk score was an independent risk factor for HCC prognosis and could be used to assess the immune status of the HCC microenvironment.

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Section: Introductionmentioning

confidence: 99%

A New Inflammation-Related Risk Model for Predicting Hepatocellular Carcinoma Prognosis

Xing

2022

BioMed Research International

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“…Importantly, GO and KEGG analysis also revealed that C1QBP was highly associated with the ribosome-related process ( Figure S5 ). Considering the importance of immune cell infiltration in HCC progression 29 , we evaluated the correlation between C1QBP expression and immune cell infiltration which was score by multiple algorithms. However, no difference was observed in HCC patents stratified by C1QBP expression (Figure 8 A and 8 B) and there were only weak to no correlations between C1QBP expression and the infiltration of immune cells or known immune genes ( Figure S6 and Figure S7 ), suggesting that immune filtration may not be involved in the roles of C1QBP during HCC progression, at least based on the data from this bioinformatic quantification.…”

Section: Resultsmentioning

confidence: 99%

The Mitochondrial Protein C1QBP Promotes Hepatocellular Carcinoma Progression by Enhancing Cell Survival, Migration and Invasion

Hou¹,

Lu²,

Wang³

et al. 2022

J. Cancer

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Backgrounds: Hepatocellular carcinoma (HCC) is a major type of death-causing cancer whose pathological mechanisms are not fully understood. In addition, the identification of effective biomarkers for HCC prognosis is in emergency. Although a variety of studies have shown that Complement C11 binding protein (C1QBP) may play a tumor-promoting or tumor-suppressive role in cancer, the functions and mechanisms of C1QBP in HCC progression are under-investigating. Methods and results: Bioinformatic approaches were employed for checking the expression of C1QBP in HCC patient samples and the association between C1QBP mRNA expression and survival rates of patients with HCC or the promoter methylation of C1QBP . MTT analysis, PI/Annexin V staining, transwell and metabolic flux assays were performed to examine the effects of C1QBP on proliferation, apoptosis, migration, invasion, and oxidative phosphorylation of HCC cells. In the present study, we observed that C1QBP is lower expressed in HCC samples and cell lines. Moreover, high levels of C1QBP were associated with unfavorable outcomes of HCC patients. Loss-of-function assays showed that proliferation, migration and invasion of HCC cells were mitigated while cell apoptosis was augmented upon the loos of C1QBP. Moreover, the oxidative phosphorylation was moderately decreased when C1QBP was depleted. Furthermore, we also investigated the methylation status and copy number variation of C1QBP and analyzed their correlation with its mRNA expression in HCC patients. Finally, we suggested that C1QBP is correlated with genes encoding ribosome RPL-related proteins and mitochondrial MRPL-related proteins in HCC patients. Conclusions: C1QBP is correlated with a poor prognosis of HCC patients and promotes the survival, migration and invasion of HCC cells.

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“…Paradoxically, we found that tumor suppressors were negatively correlated with the infiltration of pDCs, DCs, and cytotoxic cells, and the tumor promoters METTL3, VIRMA, and CBLL1 were positively correlated with Tcm and Th2 cell infiltration. Infiltration of DCs, Tcm and their derived cytotoxic T cells, along with Th2 cells, are generally considered to be protective factors for HCC ( Foerster et al, 2018 ; Lawal et al, 2021 ), which may be related to changes in the balance between DC subsets or T effector cells and regulatory T cells in tumors ( Lawal et al, 2021 ; Gao et al, 2007 ), suggesting that stratification of immune cell infiltration is the key to achieving effective treatments. Therefore, the interplay between the m 6 A writer complex and tumor microenvironment may be an important mechanism for the tumorigenesis and progression of HCC.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic, Therapeutic, and Prognostic Value of the m6A Writer Complex in Hepatocellular Carcinoma

Zhao

et al. 2022

Front. Cell Dev. Biol.

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Hepatocellular carcinoma (HCC) has poor prognosis and is usually diagnosed only at an advanced stage. Identification of novel biomarkers is critical to early diagnosis and better prognosis for HCC patients. N6-methyladenosine (m6A) RNA methylation regulators play important roles in the development of many tumors. However, the m6A writer complex, a key executor of m6A methylation modification, has not been independently investigated, and its specific bioinformatics analysis has not yet been performed in HCC. In this study, we used multiple public databases to evaluate the diagnostic, therapeutic, and prognostic value of the m6A writers in HCC. The results showed that expression levels of METTL3, VIRMA and CBLL1 were significantly increased, while expression levels of METTL14 and ZC3H13 were significantly decreased in HCC, which was closely related to clinicopathological factors, such as tumor stage and prognosis. Bioinformatics further explored the possible underlying mechanisms by which the m6A writer complex are involved in activation of tumor-promoting pathways and/or inhibition of tumor-suppressing pathways, including apoptosis, cell cycle, DNA damage response and EMT. Furthermore, we showed that the m6A writer complex is correlated with immune cell infiltration and immunoregulator expression in HCC. In conclusion, the m6A writer complex may represent a promising biomarker and target that can guide targeted therapy or immunotherapy for HCC patients.

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The Immunology of Hepatocellular Carcinoma

Cited by 51 publications

References 101 publications

A New Inflammation-Related Risk Model for Predicting Hepatocellular Carcinoma Prognosis

A New Inflammation-Related Risk Model for Predicting Hepatocellular Carcinoma Prognosis

The Mitochondrial Protein C1QBP Promotes Hepatocellular Carcinoma Progression by Enhancing Cell Survival, Migration and Invasion

Diagnostic, Therapeutic, and Prognostic Value of the m6A Writer Complex in Hepatocellular Carcinoma

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