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三阴性乳腺癌的肿瘤突变负担和免疫浸润特征:全基因组高通量数据分析。

Tumor Mutation Burden and Immune Invasion Characteristics in Triple Negative Breast Cancer: Genome High-Throughput Data Analysis.

机构信息

College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

College of Basic Medical, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Front Immunol. 2021 Apr 21;12:650491. doi: 10.3389/fimmu.2021.650491. eCollection 2021.


DOI:10.3389/fimmu.2021.650491
PMID:33968045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8097167/
Abstract

In recent years, the emergence of immunotherapy has provided a new perspective for the treatment and management of triple-negative breast cancer (TNBC). However, the relationship between tumor mutation burden (TMB) and immune infiltration and the prognosis of TNBC remains unclear. In this study, to explore the immunogenicity of TNBC, we divided patients with TNBC into high and low TMB groups based on the somatic mutation data of TNBC in The Cancer Genome Atlas (TCGA), and screened out genes with mutation rate ≥10. Then, Kaplan-Meier survival analysis revealed that the 5-year survival rate of the high TMB group was much higher than that of the low TMB group and the two groups also showed differences in immune cell infiltration. Further exploration found that the FAT3 gene, which displays significant difference and a higher mutation rate between the two groups, is not only significantly related to the prognosis of TNBC patients but also exhibits difference in immune cell infiltration between the wild group and the mutant group of the FAT3 gene. The results of gene set enrichment analysis and drug sensitivity analysis further support the importance of the FAT3 gene in TNBC. This study reveals the characteristics of TMB and immune cell infiltration in triple-negative breast cancer and their relationship with prognosis, to provide new biomarkers and potential treatment options for the future treatment of TNBC. The FAT3 gene, as a risk predictor gene of TNBC, is considered a potential biological target and may provide new insight for the treatment of TNBC.

摘要

近年来,免疫疗法的出现为三阴性乳腺癌(TNBC)的治疗和管理提供了新的视角。然而,肿瘤突变负担(TMB)与免疫浸润以及 TNBC 预后之间的关系仍不清楚。在这项研究中,为了探索 TNBC 的免疫原性,我们根据 TNBC 在 The Cancer Genome Atlas(TCGA)中的体细胞突变数据,将 TNBC 患者分为高 TMB 组和低 TMB 组,并筛选出突变率≥10%的基因。然后,Kaplan-Meier 生存分析显示,高 TMB 组的 5 年生存率明显高于低 TMB 组,两组在免疫细胞浸润方面也存在差异。进一步探索发现,FAT3 基因在两组之间差异显著且突变率较高,不仅与 TNBC 患者的预后显著相关,而且在 FAT3 基因野生型和突变型组之间的免疫细胞浸润也存在差异。基因集富集分析和药物敏感性分析的结果进一步支持了 FAT3 基因在 TNBC 中的重要性。本研究揭示了 TMB 和免疫细胞浸润在三阴性乳腺癌中的特征及其与预后的关系,为未来 TNBC 的治疗提供了新的生物标志物和潜在的治疗选择。FAT3 基因作为 TNBC 的风险预测基因,被认为是一个潜在的生物靶点,可能为 TNBC 的治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/3a3cd5853fd7/fimmu-12-650491-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/1cc0c5f46201/fimmu-12-650491-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/509948c68147/fimmu-12-650491-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/17ef64768235/fimmu-12-650491-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/5dc463255836/fimmu-12-650491-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/314e3e40d663/fimmu-12-650491-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/3a3cd5853fd7/fimmu-12-650491-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/1cc0c5f46201/fimmu-12-650491-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/509948c68147/fimmu-12-650491-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/17ef64768235/fimmu-12-650491-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/5dc463255836/fimmu-12-650491-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/314e3e40d663/fimmu-12-650491-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cff1/8097167/3a3cd5853fd7/fimmu-12-650491-g006.jpg

相似文献

[1]
Tumor Mutation Burden and Immune Invasion Characteristics in Triple Negative Breast Cancer: Genome High-Throughput Data Analysis.

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[2]
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[4]
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[6]
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[7]
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[8]
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引用本文的文献

[1]
Discovery of a new mitophagy-related gene signature for predicting the outlook and immunotherapy in triple-negative breast cancer.

Sci Rep. 2025-2-25

[2]
Identification of genes predicting chemoresistance and short survival in ovarian cancer.

Transl Cancer Res. 2024-8-31

[3]
Prognostic and Therapeutic Implications of Cell Division Cycle 20 Homolog in Breast Cancer.

Cancers (Basel). 2024-7-15

[4]
Tumour mutation burden and infiltrating immune cell subtypes influenced the breast cancer prognosis.

Transl Cancer Res. 2024-5-31

[5]
Modulatory Effects of XIAOPI Formula on CXCL1 and Selected Outcomes in Triple-Negative Breast Cancer: A Randomized Controlled Clinical Trial.

Breast Cancer (Dove Med Press). 2024-5-31

[6]
Tislelizumab: an effective treatment option for early-stage triple-negative breast cancer.

Transl Breast Cancer Res. 2023-11-22

[7]
Artificial Intelligence for Precision Oncology of Triple-Negative Breast Cancer: Learning from Melanoma.

Cancers (Basel). 2024-2-6

[8]
Neutrophil extracellular trap-associated risk index for predicting outcomes and response to Wnt signaling inhibitors in triple-negative breast cancer.

Sci Rep. 2024-2-20

[9]
Predictive biomarkers of response and survival following immunotherapy with a PD-L1 inhibitor benmelstobart (TQB2450) and antiangiogenic therapy with a VEGFR inhibitor anlotinib for pretreated advanced triple negative breast cancer.

Signal Transduct Target Ther. 2023-11-17

[10]
Identification of immune infiltration-related biomarkers in carotid atherosclerotic plaques.

Sci Rep. 2023-8-29

本文引用的文献

[1]
Liquid Biopsies to Evaluate Immunogenicity of Gynecological/Breast Tumors: On the Way to Blood-Based Biomarkers for Immunotherapies.

Breast Care (Basel). 2020-10

[2]
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Future Oncol. 2021-2

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Int J Med Sci. 2020

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Tumor mutation burden and gene alteration are associated with short disease-free survival in locally advanced triple-negative breast cancer.

Ann Transl Med. 2020-9

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Lancet Oncol. 2020-9-10

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Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer.

Front Mol Biosci. 2020-7-21

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Cancer Cell Int. 2020-8-5

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Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients.

Cancers (Basel). 2020-7-28

[10]
Upregulation of mesothelial genes in ovarian carcinoma cells is associated with an unfavorable clinical outcome and the promotion of cancer cell adhesion.

Mol Oncol. 2020-9

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