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Screening and Verification of Key Ubiquitination Genes Related to Immune Infiltration in Stage III/IV Hepatocellular Carcinoma.

作者信息

Tang Yuhong, Cao Jun, Peng Rui, Mao Xingkang, Su Bingbing, Tang Hao, Tu Daoyuan, Zhou Jie, Jiang Guoqing, Jin Shengjie, Wang Qian, Zhang Chen, Liu Renjie, Zhang Chi, Bai Dousheng

机构信息

Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, People's Republic of China.

The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China.

出版信息

J Hepatocell Carcinoma. 2023 May 22;10:765-781. doi: 10.2147/JHC.S407536. eCollection 2023.

DOI:10.2147/JHC.S407536
PMID:37250505
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10216869/
Abstract

INTRODUCTION: Immune checkpoint therapy (ICIs) effectively improves the prognosis of advanced (stage III/IV) hepatocellular carcinoma (HCC) patients. However, its objective response rate (ORR) is below 20%, significantly limiting ICI use in advanced HCC patients. The level of tumour immune infiltration influences ICI response rate. Recent studies have found ubiquitinase to be an important factor that regulates tumour immune infiltration. Therefore, the aim of this study is to explore the key ubiquitination genes that regulate immune infiltration in advanced HCC and further validate them. METHODS: A biotechnological process was performed as a means of classifying 90 advanced HCC patients into three immune subtypes and identifying associations with immune infiltration in the co-expressed modules. Ubiquitination-related genes were then screened with WGCNA. Gene enrichment analysis was performed for the target module and 30 hub genes were screened out by protein-protein interaction network (PPI). ssGSEA, single-gene sequencing and the MCP counter were used for exploring immune infiltration. TIDE score was applied for predicting drug efficacy and GSEA was used for exploring potential pathways. Finally, GRB2 expression in HCC tissue was validated by in vitro experiments. RESULTS: GRB2 expression was found to have a significant correlation with the pathological stage and prognosis of HCC patients and a positive correlation with immune infiltration and tumour mutation burden (TMB). In addition, significant correlations with the efficacy of ICIs, sorafenib and transarterial chemoembolization (TACE) were identified. GRB2 was found to be most significantly associated with the JAK-STAT signalling pathway and cytosolic DNA sensing pathway. Finally, it was found that GRB2 expression is closely related to the prognosis, tumour size and TMN stage. CONCLUSION: A significant association was observed between the ubiquitinated gene GRB2 and the prognosis and immune infiltration of advanced HCC patients and it may potentially be used for predicting therapy efficacy in advanced HCC patients in the future.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/4c4da1193e65/JHC-10-765-g0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/9a0d55c98880/JHC-10-765-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/9d5b46a76690/JHC-10-765-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/c1b6216555bd/JHC-10-765-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/3c2d1d3bcdf2/JHC-10-765-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/a34363e8bc16/JHC-10-765-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/9403e17d29d0/JHC-10-765-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/fc6f3d2704a0/JHC-10-765-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/148cf7e5a0f6/JHC-10-765-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/351a444ecdcc/JHC-10-765-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/a1600798453e/JHC-10-765-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/af4dd8bd8bb9/JHC-10-765-g0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/4c4da1193e65/JHC-10-765-g0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/9a0d55c98880/JHC-10-765-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/9d5b46a76690/JHC-10-765-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/c1b6216555bd/JHC-10-765-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/3c2d1d3bcdf2/JHC-10-765-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/a34363e8bc16/JHC-10-765-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/9403e17d29d0/JHC-10-765-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/fc6f3d2704a0/JHC-10-765-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/148cf7e5a0f6/JHC-10-765-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/351a444ecdcc/JHC-10-765-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/a1600798453e/JHC-10-765-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/af4dd8bd8bb9/JHC-10-765-g0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9a2/10216869/4c4da1193e65/JHC-10-765-g0012.jpg

相似文献

[1]
Screening and Verification of Key Ubiquitination Genes Related to Immune Infiltration in Stage III/IV Hepatocellular Carcinoma.

J Hepatocell Carcinoma. 2023-5-22

[2]
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[3]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Clinical Efficacy of Transcatheter Arterial Chemoembolization Combined With Percutaneous Microwave Coagulation Therapy for Advanced Hepatocellular Carcinoma.

Gastroenterology Res. 2024-8

本文引用的文献

[1]
Bioinformatics analysis of immune infiltrates and tripartite motif () family genes in hepatocellular carcinoma.

J Gastrointest Oncol. 2022-8

[2]
Sorafenib combined with STAT3 knockdown triggers ER stress-induced HCC apoptosis and cGAS-STING-mediated anti-tumor immunity.

Cancer Lett. 2022-10-28

[3]
Recurrent somatic mutations as predictors of immunotherapy response.

Nat Commun. 2022-7-8

[4]
Tumor cell-derived exosome RNF126 affects the immune microenvironment and promotes nasopharyngeal carcinoma progression by regulating PTEN ubiquitination.

Apoptosis. 2022-8

[5]
Concurrent High PD-L1 Expression and CD8 Immune Cell Infiltration Predict PD-1 Blockade Efficacy in Advanced EGFR-Mutant NSCLC Patients.

Clin Lung Cancer. 2022-9

[6]
Development and Validation of TACE Refractoriness-Related Diagnostic and Prognostic Scores and Characterization of Tumor Microenvironment Infiltration in Hepatocellular Carcinoma.

Front Immunol. 2022

[7]
CXCR4-guided liposomes regulating hypoxic and immunosuppressive microenvironment for sorafenib-resistant tumor treatment.

Bioact Mater. 2022-1-20

[8]
The Functional Roles of Immune Cells in Primary Liver Cancer.

Am J Pathol. 2022-6

[9]
TP53 Mutation Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration in Breast Cancer.

Front Cell Dev Biol. 2021-11-30

[10]
The Immunology of Hepatocellular Carcinoma.

Vaccines (Basel). 2021-10-15

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