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FUT8在肺腺癌和肺鳞癌中的诊断、预后及免疫作用

Diagnostic, prognostic, and immunological roles of FUT8 in lung adenocarcinoma and lung squamous cell carcinoma.

作者信息

Li Zhijun, Zhu Zhenpeng, Wang Peng, Hou Chenyang, Ren Lijuan, Xu Dandan, Wang Xiran, Guo Fei, Meng Qingxue, Liang Weizheng, Xue Jun, Zhi Xuejun

机构信息

Hebei North University, Zhangjiakou City, Hebei Province, China.

Hebei Key Laboratory of Systems Biology and Gene Regulation, Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei Province, China.

出版信息

PLoS One. 2025 May 15;20(5):e0321756. doi: 10.1371/journal.pone.0321756. eCollection 2025.


DOI:10.1371/journal.pone.0321756
PMID:40373023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12080848/
Abstract

Lung cancer remains the leading cause of malignant tumors worldwide in terms of the incidence and mortality, posing a significant threat to human health. Given that distant metastases typically occur at the time of initial diagnosis, leading to a poor 5-year survival rate among patients, it is crucial to identify markers for diagnosis, prognosis, and therapeutic efficacy monitoring. Abnormal glycosylation is a hallmark of cancer cells, characterized by the disruption of core fucosylation, which is predominantly driven by the enzyme fucosyltransferase 8 (FUT8). Evidence indicates that FUT8 is a pivotal enzyme in cancer onset and progression, influencing cellular glycosylation pathways. Utilizing bioinformatics approaches, we have investigated FUT8 in lung cancer, resulting in a more systematic and comprehensive understanding of its role in the disease's pathogenesis. In this study, we employed bioinformatics to analyze the differential expression of FUT8 between LUAD and LUSC. We observed upregulation of FUT8 in both LUAD and LUSC, associated with unfavorable prognosis, and higher diagnostic utility in LUAD. GO/KEGG analysis revealed a primary association between LUAD and the spliceosome. Immunologically, FUT8 expression was significantly associated with immune cell infiltration and immune checkpoint activity, with a notable positive correlation with M2 macrophage infiltration. Our analysis of FUT8 indicates that it may serve as a potential biomarker for lung cancer diagnosis and prognosis, and could represent a therapeutic target for LUAD and LUSC immunotherapy.

摘要

就发病率和死亡率而言,肺癌仍然是全球范围内恶性肿瘤的主要病因,对人类健康构成重大威胁。鉴于远处转移通常在初次诊断时就已发生,导致患者的5年生存率较低,因此识别用于诊断、预后和治疗疗效监测的标志物至关重要。异常糖基化是癌细胞的一个标志,其特征是核心岩藻糖基化的破坏,这主要由岩藻糖基转移酶8(FUT8)驱动。有证据表明,FUT8是癌症发生和发展中的关键酶,影响细胞糖基化途径。利用生物信息学方法,我们对肺癌中的FUT8进行了研究,从而对其在疾病发病机制中的作用有了更系统、更全面的了解。在本研究中,我们采用生物信息学方法分析了肺腺癌(LUAD)和肺鳞癌(LUSC)之间FUT8的差异表达。我们观察到LUAD和LUSC中FUT8均上调,这与不良预后相关,且在LUAD中具有更高的诊断效用。基因本体论/京都基因与基因组百科全书(GO/KEGG)分析显示LUAD与剪接体之间存在主要关联。在免疫学方面,FUT8表达与免疫细胞浸润和免疫检查点活性显著相关,与M2巨噬细胞浸润呈显著正相关。我们对FUT8的分析表明,它可能作为肺癌诊断和预后的潜在生物标志物,并且可能代表LUAD和LUSC免疫治疗的一个靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/d9638a8a00b5/pone.0321756.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/57af83b93955/pone.0321756.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/f5f087b13a4e/pone.0321756.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/48a867612bb6/pone.0321756.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/3004647122ce/pone.0321756.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/9bd1bac6bf7b/pone.0321756.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/17bdbec11093/pone.0321756.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/60db3a7f5a22/pone.0321756.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/a4ac317b436a/pone.0321756.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/49f0402bab7a/pone.0321756.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/d9638a8a00b5/pone.0321756.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/57af83b93955/pone.0321756.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/f5f087b13a4e/pone.0321756.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/48a867612bb6/pone.0321756.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/3004647122ce/pone.0321756.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/9bd1bac6bf7b/pone.0321756.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/17bdbec11093/pone.0321756.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/60db3a7f5a22/pone.0321756.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/a4ac317b436a/pone.0321756.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/49f0402bab7a/pone.0321756.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc43/12080848/d9638a8a00b5/pone.0321756.g010.jpg

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[1]
Diagnostic, prognostic, and immunological roles of FUT8 in lung adenocarcinoma and lung squamous cell carcinoma.

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[7]
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[8]
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[9]
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本文引用的文献

[1]
Research trends in lung cancer and the tumor microenvironment: a bibliometric analysis of studies published from 2014 to 2023.

Front Oncol. 2024-7-31

[2]
An update to experimental and clinical aspects of tumor-associated macrophages in cancer development: hopes and pitfalls.

Clin Exp Med. 2024-7-13

[3]
Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

CA Cancer J Clin. 2024

[4]
FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression.

Int J Oral Sci. 2024-3-28

[5]
EGFR core fucosylation, induced by hepatitis C virus, promotes TRIM40-mediated-RIG-I ubiquitination and suppresses interferon-I antiviral defenses.

Nat Commun. 2024-1-22

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Beyond antibody fucosylation: α-(1,6)-fucosyltransferase (Fut8) as a potential new therapeutic target for cancer immunotherapy.

Antib Ther. 2023-3-2

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Cancer Lett. 2023-5-28

[10]
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Nucleic Acids Res. 2023-1-6

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