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在泛癌分析中,EXO1作为一种用于预后、免疫浸润和免疫治疗的潜在生物标志物。

EXO1 as a potential biomarker for prognosis, immune infiltration, and immunotherapy in pan-cancer analysis.

作者信息

Wang Jikang, Wang Fubo, Huang Haoxuan

机构信息

Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China.

Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, 530021, China.

出版信息

Funct Integr Genomics. 2025 Apr 11;25(1):87. doi: 10.1007/s10142-025-01586-1.

DOI:10.1007/s10142-025-01586-1
PMID:40214853
Abstract

Human EXO1 is a 5' → 3' exonuclease that plays a critical role in regulating cell cycle checkpoints, maintaining replication forks and participating in post-replication DNA repair pathways. Previous studies have highlighted the importance of EXO1 in cancers such as liver and breast cancer. However, there is a gap in the comprehensive analysis of EXO1 in a wide range of cancers, and its precise role in cancer patient prognosis and immune response remains unclear. This study aims to systematically investigate the potential associations between EXO1, immune infiltration and prognostic value in different cancer types and to gain a deeper understanding of its mechanisms of action.We conducted a comprehensive investigation into the overarching role of EXO1 across various cancers by utilizing multiple databases. Our analysis encompassed scrutinizing EXO1 expression and evaluating its correlation with clinical survival, immune checkpoints, Tumor Stemness Score, Prognostic Value, immunomodulators, genomic profiles, immunological characteristics, immunotherapy, and functional enrichment. EXO1 is expressed in various normal tissues and at significantly higher levels in most tumors compared to non-tumor tissues. High EXO1 expression is associated with poor prognosis in certain cancers. Genetic mutations and RNA modifications of EXO1 were also investigated, as well as its correlation with tumor immunity and genomic stability. We investigated the potential role of EXO1 in immunotherapy and identified differing drug responses based on EXO1 expression levels in Skin Cutaneous Melanoma (SKCM), which holds promise for personalized treatment. Furthermore, we analyzed EXO1-related genes and pathways, revealing its potential involvement in crucial biological processes such as DNA repair and cell cycle regulation. These findings provide a comprehensive understanding of the role of EXO1 in cancer initiation and progression, offering valuable insights for personalized cancer therapy and precision medicine. This study highlights the diverse functions of EXO1 in cancer, including its involvement in cancer initiation, prognosis, immune regulation, and response to immunotherapy. These findings provide valuable insights into the potential of EXO1 as a biomarker and therapeutic target, as well as its role in determining treatment response in cancer management. This information is crucial for guiding personalized cancer therapy and precision medicine.

摘要

人源EXO1是一种5' → 3'核酸外切酶,在调节细胞周期检查点、维持复制叉以及参与复制后DNA修复途径中发挥关键作用。先前的研究强调了EXO1在肝癌和乳腺癌等癌症中的重要性。然而,对EXO1在多种癌症中的综合分析存在空白,其在癌症患者预后和免疫反应中的精确作用仍不清楚。本研究旨在系统地探究EXO1、免疫浸润与不同癌症类型预后价值之间的潜在关联,并更深入地了解其作用机制。我们利用多个数据库对EXO1在各种癌症中的总体作用进行了全面研究。我们的分析包括仔细研究EXO1的表达,并评估其与临床生存、免疫检查点、肿瘤干性评分、预后价值、免疫调节剂、基因组图谱、免疫特征、免疫治疗以及功能富集的相关性。EXO1在各种正常组织中均有表达,与非肿瘤组织相比,在大多数肿瘤中的表达水平显著更高。EXO1高表达与某些癌症的不良预后相关。我们还研究了EXO1的基因突变和RNA修饰,以及其与肿瘤免疫和基因组稳定性的相关性。我们研究了EXO1在免疫治疗中的潜在作用,并基于皮肤黑色素瘤(SKCM)中EXO1的表达水平确定了不同的药物反应,这为个性化治疗带来了希望。此外,我们分析了与EXO1相关的基因和途径,揭示了其可能参与DNA修复和细胞周期调控等关键生物学过程。这些发现全面了解了EXO1在癌症发生和发展中的作用,为个性化癌症治疗和精准医学提供了有价值的见解。本研究强调了EXO1在癌症中的多种功能,包括其参与癌症发生、预后、免疫调节以及对免疫治疗的反应。这些发现为EXO1作为生物标志物和治疗靶点的潜力,以及其在确定癌症治疗反应中的作用提供了有价值的见解。这些信息对于指导个性化癌症治疗和精准医学至关重要。

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Funct Integr Genomics. 2025 Apr 11;25(1):87. doi: 10.1007/s10142-025-01586-1.
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本文引用的文献

1
Emerging role of RNA modification and long noncoding RNA interaction in cancer.RNA 修饰和长非编码 RNA 相互作用在癌症中的新兴作用。
Cancer Gene Ther. 2024 Jun;31(6):816-830. doi: 10.1038/s41417-024-00734-2. Epub 2024 Feb 14.
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Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer.多组学分析揭示了泛癌早期复发和早期转移的分子图景。
Front Genet. 2023 Apr 20;14:1061364. doi: 10.3389/fgene.2023.1061364. eCollection 2023.
3
Exonuclease 1 is a Potential Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma.
核酸外切酶1是肝细胞癌潜在的诊断和预后生物标志物。
Front Mol Biosci. 2022 Jun 13;9:889414. doi: 10.3389/fmolb.2022.889414. eCollection 2022.
4
Role of main RNA modifications in cancer: N-methyladenosine, 5-methylcytosine, and pseudouridine.主要 RNA 修饰在癌症中的作用:N6-甲基腺苷、5-甲基胞嘧啶和假尿嘧啶。
Signal Transduct Target Ther. 2022 Apr 28;7(1):142. doi: 10.1038/s41392-022-01003-0.
5
Inhibitors of immune checkpoints-PD-1, PD-L1, CTLA-4-new opportunities for cancer patients and a new challenge for internists and general practitioners.免疫检查点抑制剂-PD-1、PD-L1、CTLA-4-为癌症患者带来新机遇,也为内科医生和全科医生带来新挑战。
Cancer Metastasis Rev. 2021 Sep;40(3):949-982. doi: 10.1007/s10555-021-09976-0. Epub 2021 Jul 8.
6
Combination of CTLA-4 and PD-1 blockers for treatment of cancer.CTLA-4 和 PD-1 抑制剂联合治疗癌症。
J Exp Clin Cancer Res. 2019 Jun 13;38(1):255. doi: 10.1186/s13046-019-1259-z.
7
Next generation of immune checkpoint therapy in cancer: new developments and challenges.癌症免疫检查点治疗的新一代:新进展与新挑战。
J Hematol Oncol. 2018 Mar 15;11(1):39. doi: 10.1186/s13045-018-0582-8.
8
Cell cycle-dependent control of homologous recombination.同源重组的细胞周期依赖性调控。
Acta Biochim Biophys Sin (Shanghai). 2017 Aug 1;49(8):655-668. doi: 10.1093/abbs/gmx055.
9
Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisions.Exo1 在人类的 DNA 末端切除中起着重要作用,并影响双链断裂修复和损伤信号转导的决策。
DNA Repair (Amst). 2012 Apr 1;11(4):441-8. doi: 10.1016/j.dnarep.2012.01.006. Epub 2012 Feb 11.
10
Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation.Exo1 与修复合成竞争,将 NER 中间体转化为长单链 DNA 缺口,并促进检查点激活。
Mol Cell. 2010 Oct 8;40(1):50-62. doi: 10.1016/j.molcel.2010.09.004.