共激活因子相关精氨酸甲基转移酶1的表达与泛癌预后及免疫微环境的相关性分析
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1.安徽医科大学基础医学院 病理学与病理生理学系;2.首都医科大学基础医学院 生物化学与分子生物学系,北京 100069;3.芜湖市第二人民医院 肿瘤科

作者简介:

平苗苗,安徽医科大学基础医学院/首都医科大学基础医学院博士研究生,主要从事肿瘤代谢重编程方面的研究。

基金项目:

国家自然科学基金资助项目(82002598)。


Expression of coactivator-associated arginine methyltransferase 1 and its correlation with pan-cancer prognosis and immune microenvironment
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1.Department of Pathology and Pathophysiology, School of Basic Medical Science, Anhui Medical University, Hefei 230032, China;2.Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;3.Department of Oncology, the Second People's Hospital of Wuhu, Wuhu, Anhui 241001, China

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    摘要:

    背景与目的 共激活因子相关精氨酸甲基转移酶1(CARM1)参与调节RNA和蛋白质的加工。最近的研究揭示其在肿瘤发生和发展中扮演着重要作用。然而,目前仍缺乏CARM1的表达与泛癌预后和免疫微环境的相关性研究。本研究通过生物信息学方法探讨CARM1的表达与泛癌预后和免疫微环境的相关性及其潜在的生物学机制。方法 使用TCGA、GTEx、HPA数据库探索CARM1在泛癌中的表达情况及其与预后的关系;利用TCGA数据库分析CARM1与泛癌的肿瘤微环境、免疫检查点基因的相关性;通过STRING数据库探讨CARM1互作基因的PPI网络;采用GSEA研究CARM1在泛癌中的潜在生物学机制。结果 与正常组织相比,CARM1在多数肿瘤组织中的表达水平上调,CARM1的表达与多种肿瘤的预后相关;CARM1的表达与免疫细胞的浸润和免疫检查点的表达相关;富集分析表明CARM1可能通过影响核糖体生物合成改变泌尿系统肿瘤生物学功能;通过影响精氨酸生物合成、DNA复制和细胞周期等影响消化系统肿瘤生物学功能。结论 CARM1在肿瘤组织中异常表达,可能作为多种肿瘤的预后标志物,与泛癌的肿瘤微环境和免疫检查点基因的表达相关,可能通过多种生物学途径参与肿瘤的发生发展,是泛癌治疗的潜在靶点。

    Abstract:

    Background and Aims Coactivator-associated arginine methyltransferase 1 (CARM1) is involved in the regulation of RNA and protein processing. Recent studies have revealed its crucial role in tumorigenesis and cancer progression. However, the correlation between CARM1 expression, pan-cancer prognosis, and the immune microenvironment remains unclear. This study was conducted to investigate the relationship between CARM1 expression and pan-cancer prognosis, immune microenvironment, and its potential biological mechanisms using bioinformatics approaches.Methods Using the TCGA, GTEx, and HPA databases, the expression pattern of CARM1 in various cancers and its prognostic relevance were analyzed. The correlation between CARM1 expression and the tumor microenvironment, as well as immune checkpoint genes, were analyzed using TCGA data. The PPI network of CARM1-interacting genes was constructed using the STRING database. GSEA was performed to investigate the potential biological mechanisms of CARM1 in pan-cancer.Results Compared to normal tissues, CARM1 was upregulated in most tumor tissues, and its expression was associated with prognosis in multiple cancers. CARM1 expression was correlated with immune cell infiltration and immune checkpoint gene expression. Enrichment analysis suggested that CARM1 might alter the biological function of urinary system tumors by affecting ribosome biogenesis. Additionally, it may influence the biological functions of digestive system tumors by modulating arginine biosynthesis, DNA replication, and the cell cycle.Conclusion CARM1 is aberrantly expressed in tumor tissues and may serve as a prognostic biomarker for multiple cancers. It is associated with the tumor microenvironment and immune checkpoint gene expression in pan-cancer and may contribute to tumorigenesis through multiple biological pathways, making it a potential therapeutic target for pan-cancer treatment.

    图1 CARM1在泛癌中的表达 A:TCGA数据库中,CARM1在34种肿瘤中的表达情况;B:TCGA结合GTEx数据库,CARM1在34种肿瘤中的表达情况;C:HPA数据库中CARM1蛋白的免疫组化染色Fig.1 The expression of CARM1 in pan-cancer A: Analyze the expression of CARM1 in 34 types of tumors based in the TCGA database; B: Combine the TCGA and GTEx databases to analyze the expression of CARM1 in 34 types of tumors; C: Immunohistochemistry staining of CARM1 protein in the HPA database
    图2 CARM1的表达与8种肿瘤预后的关系 A:OS;B:DSSFig.2 The relationship between CARM1 expression and prognosis in eight types of cancer A: OS; B: DSS
    图3 CARM1表达与TMB及MSI的相关性Fig.3 The associations of CARM1 expression with TMB and MSI
    图4 CARM1与肿瘤微环境的相关性Fig.4 The correlation between CARM1 and the tumor microenvironment
    图5 CARM1与免疫浸润及免疫检查点基因表达的相关性 A:CARM1的表达与4种肿瘤免疫细胞浸润情况的相关性;B:在泛癌中CARM1的表达与免疫检查点基因表达的关系Fig.5 Correlation between CARM1 and immune infiltration as well as immune checkpoint gene expression A: Correlation between CARM1 expression and immune cell infiltration in four types of cancer; B: Relationship between CARM1 expression and immune checkpoint gene expression in pan-cancer
    图6 CARM1互作蛋白分析 A:通过STRING数据库获得与CARM1相互作用的PPI;B:STRING数据库和GEPIA分析得到CARM1潜在互作基因Fig.6 Analysis of CARM1-interacting proteins A: PPI network of CARM1-interacting proteins obtained from the STRING database; B: Potential CARM1-interacting genes identified through STRING and GEPIA analysis
    图7 CARM1通路富集分析 A:CARM1的KEGG富集分析和GSEA基于Hallmark进行的富集分析;B:不同系统肿瘤的潜在共同生物学机制Fig.7 Pathway enrichment analysis of CARM1 A: KEGG enrichment analysis of CARM1 and GSEA enrichment analysis based on Hallmark gene sets; B: Potential common biological mechanisms in different system tumors
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平苗苗,李光耀,李启娇,王星星,郭继政.共激活因子相关精氨酸甲基转移酶1的表达与泛癌预后及免疫微环境的相关性分析[J].中国普通外科杂志,2025,34(3):516-527.
DOI:10.7659/j. issn.1005-6947.240121

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  • 收稿日期:2024-03-04
  • 最后修改日期:2025-03-15
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  • 在线发布日期: 2025-04-14