Wang Jingyun, Liu Fen, Heng Jianfu, Li Guoli
Department of Obstetrics and Gynecology, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, China.
Department of Obstetrics and Gynecology, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University (The First Hospital of Changsha), Changsha, China.
Mamm Genome. 2025 Mar;36(1):262-279. doi: 10.1007/s00335-024-10092-x. Epub 2024 Dec 24.
Exonuclease 1 (EXO1) is an evolutionarily conserved exonuclease, which have function on maintaining genomic stability. Elevated expression of EXO1 has been reported in certain cancers. However, a comprehensive pan-cancer analysis of EXO1 is still lacking and its role in human cancer development remains poorly understood. This study aims to investigate the genetic alterations and expression perturbations of EXO1 and evaluate its potential clinical relevance in different cancer types. By employing powerful bioinformatics tools and utilizing data sourced from The Cancer Genome Atlas and the Genotype-Tissue Expression datasets, a comprehensive pan-cancer analysis of EXO1 was conducted, including an examination of gene expression, alterations in genetics, DNA methylation patterns, survival outcomes, clinical traits, immune features, and functional enrichment analysis. EXO1 was found to be highly expressed across 20 tumor types, including lung adenocarcinoma, lung squamous cell carcinoma, and breast invasive carcinoma. The expression levels of EXO1 are frequently associated with later clinical stages and unfavorable outcomes. Genetic alterations in EXO1 were predominantly found to be amplified in a pan-cancer context. A total of 131 missense mutations, 24 truncation mutations, 1 in-frame mutation, 6 splice site mutations, and 1 fusion mutation were identified. Interestingly, a significant co-occurrence of alterations in EXO1 with other ten gene alterations were identified. The expression of EXO1 in multiple tumors showed a significant correlation with tumor mutational burden, microsatellite instability, and genes related to immunological checkpoints. In most types of cancer, a strong correlation exists between the expression of EXO1 and the infiltration of CD4 Th2 cells, memory CD4 T cells, myeloid-derived suppressor cells, and common lymphoid progenitors. Analysis of 150 genes related to EXO1 demonstrate an enrichment in processes such as cell cycle regulation, DNA damage repair, and relevant signaling pathways, suggesting a possible mechanism through which EXO1 may facilitate tumor development. This study offers a deep insight into the role of EXO1 in different types of human cancers, indicating that EXO1 could act as an important prognostic biomarker and a therapeutic target for certain types of cancer.
核酸外切酶1（EXO1）是一种进化上保守的核酸外切酶，在维持基因组稳定性方面发挥作用。已有报道称EXO1在某些癌症中表达升高。然而，目前仍缺乏对EXO1的全面泛癌分析，其在人类癌症发展中的作用仍知之甚少。本研究旨在调查EXO1的基因改变和表达扰动，并评估其在不同癌症类型中的潜在临床相关性。通过使用强大的生物信息学工具，并利用来自癌症基因组图谱和基因型-组织表达数据集的数据，对EXO1进行了全面的泛癌分析，包括基因表达检查、基因改变、DNA甲基化模式、生存结果、临床特征、免疫特征以及功能富集分析。研究发现EXO1在20种肿瘤类型中高表达，包括肺腺癌、肺鳞状细胞癌和乳腺浸润性癌。EXO1的表达水平常与较晚的临床分期和不良预后相关。在泛癌背景下，主要发现EXO1的基因改变为扩增。共鉴定出131个错义突变、24个截短突变、1个框内突变、6个剪接位点突变和1个融合突变。有趣的是，还发现EXO1的改变与其他十种基因改变存在显著共现。EXO1在多种肿瘤中的表达与肿瘤突变负担、微卫星不稳定性以及与免疫检查点相关的基因显著相关。在大多数癌症类型中，EXO1的表达与CD4 Th2细胞、记忆性CD4 T细胞、骨髓来源的抑制细胞和普通淋巴祖细胞的浸润之间存在强烈相关性。对与EXO1相关的150个基因的分析表明，这些基因在细胞周期调控、DNA损伤修复和相关信号通路等过程中富集，提示EXO1促进肿瘤发展的可能机制。本研究深入洞察了EXO1在不同类型人类癌症中的作用，表明EXO1可能作为一种重要的预后生物标志物和某些类型癌症的治疗靶点。
