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铁死亡相关基因对肝细胞癌预后及肿瘤突变负荷的影响

The Effect of Ferroptosis-Related Genes on Prognosis and Tumor Mutational Burden in Hepatocellular Carcinoma.

作者信息

Zhang Hao, Liu Renzheng, Sun Lin, Guo Weidong, Hu Xiao

机构信息

Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Department of ICU, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

出版信息

J Oncol. 2021 Aug 18;2021:7391560. doi: 10.1155/2021/7391560. eCollection 2021.

DOI:10.1155/2021/7391560
PMID:34457006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8390157/
Abstract

In this study, we constructed the ferroptosis-related genes diagnostic and prognostic models. We analyzed the relationship between ferroptosis and tumor mutational burden in hepatocellular carcinoma (HCC). Eighty-four ferroptosis-related genes were analyzed by Cox regression and the least absolute shrinkage and selection operator method. Seven genes (SLC7A11, ACSL3, ACACA, SLC1A5, G6PD, ACSL6, and VDAC2) were used to construct models. The reliability of the model was verified by using the data from the ICGC database. Differential genes in high and low-risk groups revealed enrichment of many immune features by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The degree of ferroptosis was negatively correlated with tumor mutational burden (i.e., the higher the degree of ferroptosis, the lower the tumor mutational burden). The tumor mutational burden was negatively correlated with survival. We also found that ALB, TP53, and DOCK2 may be a bridge between ferroptosis and tumor mutational burden. The reported models and the relationship with tumor mutational burden indicate new possibilities for individualized treatment of HCC patients.

摘要

在本研究中，我们构建了铁死亡相关基因诊断和预后模型。我们分析了肝细胞癌（HCC）中铁死亡与肿瘤突变负荷之间的关系。通过Cox回归和最小绝对收缩和选择算子方法分析了84个铁死亡相关基因。使用7个基因（SLC7A11、ACSL3、ACACA、SLC1A5、G6PD、ACSL6和VDAC2）构建模型。利用国际癌症基因组联盟（ICGC）数据库的数据验证了模型的可靠性。高风险和低风险组中的差异基因通过基因本体论和京都基因与基因组百科全书揭示了许多免疫特征的富集。铁死亡程度与肿瘤突变负荷呈负相关（即铁死亡程度越高，肿瘤突变负荷越低）。肿瘤突变负荷与生存率呈负相关。我们还发现，ALB、TP53和DOCK2可能是铁死亡与肿瘤突变负荷之间的桥梁。所报道的模型以及与肿瘤突变负荷的关系为HCC患者的个体化治疗指明了新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/6c799d2bb6af/JO2021-7391560.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/8f06fc7e1c21/JO2021-7391560.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/fe9181e86cc3/JO2021-7391560.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/0e2489ba1e0e/JO2021-7391560.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/dd881e1525f3/JO2021-7391560.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/d485ddff49fc/JO2021-7391560.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/cde8a6d9bfe6/JO2021-7391560.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/6c799d2bb6af/JO2021-7391560.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/8f06fc7e1c21/JO2021-7391560.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/fe9181e86cc3/JO2021-7391560.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/0e2489ba1e0e/JO2021-7391560.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/dd881e1525f3/JO2021-7391560.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/d485ddff49fc/JO2021-7391560.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/cde8a6d9bfe6/JO2021-7391560.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efc/8390157/6c799d2bb6af/JO2021-7391560.007.jpg

相似文献

[1]
The Effect of Ferroptosis-Related Genes on Prognosis and Tumor Mutational Burden in Hepatocellular Carcinoma.

J Oncol. 2021-8-18

[2]
Integrated Analysis of Immunity- and Ferroptosis-Related Biomarker Signatures to Improve the Prognosis Prediction of Hepatocellular Carcinoma.

Front Genet. 2020-12-18

[3]
Construction and External Validation of a Ferroptosis-Related Gene Signature of Predictive Value for the Overall Survival in Bladder Cancer.

Front Mol Biosci. 2021-5-21

[4]
Ferroptosis-Related Gene-Based Prognostic Model and Immune Infiltration in Clear Cell Renal Cell Carcinoma.

Front Genet. 2021-6-9

[5]
Comprehensive analysis of ferroptosis-related gene signatures as a potential therapeutic target for acute myeloid leukemia: A bioinformatics analysis and experimental verification.

Front Oncol. 2022-8-11

[6]
Identification of Aging-Related Genes Associated With Clinical and Prognostic Features of Hepatocellular Carcinoma.

Front Genet. 2021-6-23

[7]
Development and Validation of a Combined Ferroptosis and Immune Prognostic Classifier for Hepatocellular Carcinoma.

Front Cell Dev Biol. 2020-12-23

[8]
Development and Validation of a Ferroptosis-Related Gene Signature for Overall Survival Prediction in Lung Adenocarcinoma.

Front Cell Dev Biol. 2021-7-7

[9]
Identification of ferroptosis genes in immune infiltration and prognosis in thyroid papillary carcinoma using network analysis.

BMC Genomics. 2021-7-27

[10]
Ferroptosis-Related Gene Signature and Patterns of Immune Infiltration Predict the Overall Survival in Patients With Lung Adenocarcinoma.

Front Mol Biosci. 2021-7-30

引用本文的文献

[1]
Ferroptosis and its current progress in gastric cancer.

Front Cell Dev Biol. 2024-2-28

[2]
Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma.

Int J Mol Sci. 2023-2-8

[3]
Integrated analysis of ferroptosis-related gene signature for overall survival prediction in Asian patients with hepatocellular carcinoma.

Clin Transl Oncol. 2023-3

[4]
Glutamine Transporter SLC1A5 Regulates Ionizing Radiation-Derived Oxidative Damage and Ferroptosis.

Oxid Med Cell Longev. 2022

[5]
Perspectives and mechanisms for targeting ferroptosis in the treatment of hepatocellular carcinoma.

Front Mol Biosci. 2022-8-16

[6]
A Novel Ferroptosis-Related Long Non-Coding RNA Prognostic Signature Correlates With Genomic Heterogeneity, Immunosuppressive Phenotype, and Drug Sensitivity in Hepatocellular Carcinoma.

Front Immunol. 2022

[7]
Ferroptosis: A New Strategy for Cancer Therapy.

Front Oncol. 2022-2-16

[8]
Genetic Profiles of Ferroptosis in Malignant Brain Tumors and Off-Target Effects of Ferroptosis Induction.

Front Oncol. 2021-12-1

本文引用的文献

[1]
Thymosin beta 4 alleviates non-alcoholic fatty liver by inhibiting ferroptosis via up-regulation of GPX4.

Eur J Pharmacol. 2021-10-5

[2]
Sorafenib fails to trigger ferroptosis across a wide range of cancer cell lines.

Cell Death Dis. 2021-7-13

[3]
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Cancer Invest. 2021-9

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Hepatocellular carcinoma in viral and autoimmune liver diseases: Role of CD4+ CD25+ Foxp3+ regulatory T cells in the immune microenvironment.

World J Gastroenterol. 2021-6-14

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Functional interplay among thiol-based redox signaling, metabolism, and ferroptosis unveiled by a genetic variant of .

Proc Natl Acad Sci U S A. 2020-10-14

[6]
Distinct TP53 Mutation Types Exhibit Increased Sensitivity to Ferroptosis Independently of Changes in Iron Regulatory Protein Activity.

Int J Mol Sci. 2020-9-15

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J Leukoc Biol. 2021-2

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Ferroptosis: A Novel Mechanism of Artemisinin and its Derivatives in Cancer Therapy.

Curr Med Chem. 2021

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Neoadjuvant neratinib promotes ferroptosis and inhibits brain metastasis in a novel syngeneic model of spontaneous HER2 breast cancer metastasis.

Breast Cancer Res. 2019-8-13

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