Circulating CTLA-4 levels and CTLA4 polymorphisms associate with disease condition and progression and hepatocellular carcinoma patients' survival in chronic hepatitis B virus infection

Wang, Li; Li, Na; Fan, Xiude; Wang, Xiaoyun; Zhang, Kun; Han, Qunying; Lv, Yi; Liu, Zhengwen

doi:10.1016/j.intimp.2020.106377

Cited by 13 publications

(22 citation statements)

References 36 publications

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“…Interestingly, low macrophage ( 85 ) and NK cell ( 86 ) infiltration predicted a poor prognosis in patients with HCC. High levels of ICGs, such as CTLA4 ( 87 ) and LAG3 ( 88 ), had a negative impact on the prognosis of HCC patients. HCC patients with high stemness genes tend to have more aggressive tumor growth with poor prognoses ( 89 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular subtypes and a prognostic model for hepatocellular carcinoma based on immune- and immunogenic cell death-related lncRNAs

Gao

et al. 2022

Front. Immunol.

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BackgroundAccumulating evidence shows that immunogenic cell death (ICD) enhances immunotherapy effectiveness. In this study, we aimed to develop a prognostic model combining ICD, immunity, and long non-coding RNA biomarkers for predicting hepatocellular carcinoma (HCC) outcomes.MethodsImmune- and immunogenic cell death-related lncRNAs (IICDLs) were identified from The Cancer Genome Atlas and Ensembl databases. IICDLs were extracted based on the results of differential expression and univariate Cox analyses and used to generate molecular subtypes using ConsensusClusterPlus. We created a prognostic signature based on IICDLs and a nomogram based on risk scores. Clinical characteristics, immune landscapes, immune checkpoint blocking (ICB) responses, stemness, and chemotherapy responses were also analyzed for different molecular subtypes and risk groups.ResultA total of 81 IICDLs were identified, 20 of which were significantly associated with overall survival (OS) in patients with HCC. Cluster analysis divided patients with HCC into two distinct molecular subtypes (C1 and C2), with patients in C1 having a shorter survival time than those in C2. Four IICDLs (TMEM220-AS1, LINC02362, LINC01554, and LINC02499) were selected to develop a prognostic model that was an independent prognostic factor of HCC outcomes. C1 and the high-risk group had worse OS (hazard ratio > 1.5, p < 0.01), higher T stage (p < 0.05), higher clinical stage (p < 0.05), higher pathological grade (p < 0.05), low immune cell infiltration (CD4+ T cells, B cells, macrophages, neutrophils, and myeloid dendritic cells), low immune checkpoint gene expression, poor response to ICB therapy, and high stemness. Different molecular subtypes and risk groups showed significantly different responses to several chemotherapy drugs, such as doxorubicin (p < 0.001), 5-fluorouracil (p < 0.001), gemcitabine (p < 0.001), and sorafenib (p < 0.01).ConclusionOur study identified molecular subtypes and a prognostic signature based on IICDLs that could help predict the clinical prognosis and treatment response in patients with HCC.

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Section: Discussionmentioning

confidence: 99%

Molecular subtypes and a prognostic model for hepatocellular carcinoma based on immune- and immunogenic cell death-related lncRNAs

Gao

et al. 2022

Front. Immunol.

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“…As a member of the immunoglobulin superfamily, CTLA-4 encodes a protein that transmits an inhibitory signal to T cells and is involved in the immune dysfunction of liver disease caused by HBV and HCC [ 27 ]. A previous study showed that the circulating CTLA-4 levels and the CTLA4 rs231775 polymorphism are associated with the condition and progression of chronic liver disease caused by HBV and HCC, and thus, their determination may be used for prognosis and monitoring disease progression [ 28 ]. In the present study, many immune-related genes and significant signaling pathways ( p < 0.05) were identified in the “red” co-expression module, which were closely related to the immune system and HBV-related HCC.…”

Section: Discussionmentioning

confidence: 99%

Immune-Related lncRNAs with WGCNA Identified the Function of SNHG10 in HBV-Related Hepatocellular Carcinoma

Hou

Wang

et al. 2022

Journal of Oncology

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Objective. The hepatitis B virus (HBV) infection led to hepatitis, which was one of common reasons for hepatocellular carcinoma (HCC). The immune microenvironment alteration played a crucial role in this process. The study aimed to identify immune-related long noncoding RNAs (lncRNAs) in HBV-related HCC and explore potential mechanisms. Methods. In total, 1,072 immune‐related genes (IRGs) were enriched in different co-expression modules with weighted gene co-expression network analysis (WGCNA) combining the corresponding clinical features in HBV-related HCC. The immune-related lncRNAs were selected from the crucial co-expression model based on the correlation analysis with IRGs. The immune-related lncRNAs were furtherly used to construct prognostic signature by the Cox proportional hazards regression and Lasso regression. Furthermore, the proliferation and migration ability of lncRNA SNHG10 were verified in vitro. Results. A total of nine co-expression modules were identified by WGCNA of which the “red” co-expression module was most correlated with various clinical characteristics. Additionally, the IRGs in this module were significantly enriched in multiple immune-related pathways. The twelve immune-related lncRNAs prognostic signature (HAND2-AS1, LINC00844, SNHG10, MALAT1, LINC00460, LBX2-AS1, MIR31HG, SEMA6A-AS1, LINC1278, LINC00514, CTBP-AS2, and LINC00205) was constructed. The risk score was an independent risk factor in HBV-related HCC and verified by principal components analysis (PCA), nomogram, and PCR between different cell lines. Moreover, the proportion of immune cells were significantly different between high-risk score group and low-risk score group. The malignant behavior of Hep3B was significantly different between si-lncRNA SNHG10 and control group. Conclusions. The immune-related lncRNAs prognostic signature provided some potential biomarkers and molecular mechanisms in HBV-related HCC.

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“…They also found that CTLA‐4 haplotypes may affect HCC development 57 . Additionally, the levels of CTLA‐4 and the CTLA4 rs231775 polymorphism were related to the disease condition and HCC progression during chronic HBV infection, the determination of which might monitor disease progression and predict patient prognosis 58 …”

Section: The Regulatory Signals Of Icp In the Development Of Hccmentioning

confidence: 99%

“…57 Additionally, the levels of CTLA-4 and the CTLA4 rs231775 polymorphism were related to the disease condition and HCC progression during chronic HBV infection, the determination of which might monitor disease progression and predict patient prognosis. 58 F I G U R E 2 The regulatory signals of PD-1 in hepatocellular carcinoma. Indomethacin can upregulate the expression of PD-L2 and PD-1 via the JAK/STAT3 and TRIF/NF-κB pathways, resulting in aggravated HCC.…”

Section: The Regulation Of Ctla-4 Signals In the Development Of Hccmentioning

confidence: 99%

Blockade of PD‐1 and CTLA‐4: A potent immunotherapeutic approach for hepatocellular carcinoma

Hou,

Xu,

et al. 2023

BioFactors

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Immune checkpoints (ICPs) can promote tumor growth and prevent immunity‐induced cancer cell apoptosis. Fortunately, targeting ICPs, such as programmed cell death 1 (PD‐1) or cytotoxic T lymphocyte associated protein 4 (CTLA‐4), has achieved great success in the past few years and has gradually become an effective treatment for cancers, including hepatocellular carcinoma (HCC). However, many patients do not respond to ICP therapy due to acquired resistance and recurrence. Therefore, clarifying the specific mechanisms of ICP in the development of HCC is very important for enhancing the efficacy of anti‐PD‐1 and anti‐CTLA‐4 therapy. In particular, antigen presentation and interferon‐γ (IFN‐γ) signaling were reported to be involved in the development of resistance. In this review, we have explained the role and regulatory mechanisms of ICP therapy in HCC pathology. Moreover, we have also elaborated on combinations of ICP inhibitors and other treatments to enhance the antitumor effect. Collectively, recent advances in the pharmacological targeting of ICPs provide insights for the development of a novel alternative treatment for HCC.

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Circulating CTLA-4 levels and CTLA4 polymorphisms associate with disease condition and progression and hepatocellular carcinoma patients' survival in chronic hepatitis B virus infection

Cited by 13 publications

References 36 publications

Molecular subtypes and a prognostic model for hepatocellular carcinoma based on immune- and immunogenic cell death-related lncRNAs

Molecular subtypes and a prognostic model for hepatocellular carcinoma based on immune- and immunogenic cell death-related lncRNAs

Immune-Related lncRNAs with WGCNA Identified the Function of SNHG10 in HBV-Related Hepatocellular Carcinoma

Blockade of PD‐1 and CTLA‐4: A potent immunotherapeutic approach for hepatocellular carcinoma

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