Jingyuan Luo, Qianyue Zhang, Shutong Wang, Luojie Zheng, Jie Liu, Yuchen Zhang, Yingchen Wang, Ranran Wang, Zhigang Xiao, Zheng Li
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Validation was performed using immunohistochemical staining data from the Human Protein Atlas (HPA) database and qPCR experiments. Receiver operating characteristic curve analysis and Kaplan-Meier survival analysis were conducted to assess the clinical relevance of CMPK2 expression. The Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data (ESTIMATE) algorithm and the Tumor IMmune Estimation Resource (TIMER) database were used to evaluate the correlation between CMPK2 and immune infiltration in tumors. The Tumor Immune Syngeneic Mouse (TISMO) database and other public datasets were utilized to assess the impact of CMPK2 on immune therapy response. MEXPRESS and MethSurv databases were employed to investigate the effects of methylation on CMPK2 expression.</p><p><strong>Results: </strong>CMPK2 expression was elevated in 23 cancers and decreased in two cancers. Furthermore, CMPK2 expression had a high diagnostic value for 16 cancers. Elevated CMPK2 expression was associated with lower overall survival (OS), disease-specific survival (DSS), and progression- free interval (PFI) in four cancers. Immune microenvironment-related analysis revealed strong associations between CMPK2 expression and immune cell infiltration, as well as immune checkpoint expression across various tumors. Notably, in four mouse immunotherapy cohorts, CMPK2 expression in treated mouse tumors was higher post-treatment. In five clinical immunotherapy cohorts, patients with high CMPK2 expression show better responses to immunotherapy. Moreover, the methylation level of CMPK2 gene was closely correlated to its expression and tumor prognosis. Among these cancers, the clinical and immunological indications of skin cutaneous melanoma (SKCM) are particularly closely related to CMPK2 expression.</p><p><strong>Conclusion: </strong>Our analysis preliminarily describes the complex function of CMPK2 in cancer progression and immune microenvironment, highlighting its potential as a diagnostic and therapeutic target for immunotherapy.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":"209-229"},"PeriodicalIF":2.3000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comprehensive Pan-cancer Analysis of CMPK2 as Biomarker and Prognostic Indicator for Immunotherapy.\",\"authors\":\"Jingyuan Luo, Qianyue Zhang, Shutong Wang, Luojie Zheng, Jie Liu, Yuchen Zhang, Yingchen Wang, Ranran Wang, Zhigang Xiao, Zheng Li\",\"doi\":\"10.2174/0115680096281451240306062101\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>UMP-CMP kinase 2 (CMPK2) is involved in mitochondrial DNA synthesis, which can be oxidized and released into the cytoplasm in innate immunity. It initiates the assembly of NLRP3 inflammasomes and mediates various pathological processes such as human immunodeficiency virus infection and systemic lupus erythematosus. However, the role of CMPK2 in tumor progression and tumor immunity remains unclear.</p><p><strong>Methods: </strong>We identified CMPK2 expression patterns in the Genotype Tissue-Expression (GTEx), The Cancer Genome Atlas (TCGA), and the Cancer Cell Line Encyclopedia (CCLE) databases. Validation was performed using immunohistochemical staining data from the Human Protein Atlas (HPA) database and qPCR experiments. Receiver operating characteristic curve analysis and Kaplan-Meier survival analysis were conducted to assess the clinical relevance of CMPK2 expression. The Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data (ESTIMATE) algorithm and the Tumor IMmune Estimation Resource (TIMER) database were used to evaluate the correlation between CMPK2 and immune infiltration in tumors. The Tumor Immune Syngeneic Mouse (TISMO) database and other public datasets were utilized to assess the impact of CMPK2 on immune therapy response. MEXPRESS and MethSurv databases were employed to investigate the effects of methylation on CMPK2 expression.</p><p><strong>Results: </strong>CMPK2 expression was elevated in 23 cancers and decreased in two cancers. Furthermore, CMPK2 expression had a high diagnostic value for 16 cancers. Elevated CMPK2 expression was associated with lower overall survival (OS), disease-specific survival (DSS), and progression- free interval (PFI) in four cancers. 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引用次数: 0
摘要
简介UMP-CMP 激酶 2(CMPK2)参与线粒体 DNA 的合成,在先天性免疫过程中,线粒体 DNA 可被氧化并释放到细胞质中。它能启动 NLRP3 炎症小体的组装,并介导各种病理过程,如人类免疫缺陷病毒感染和系统性红斑狼疮。然而,CMPK2在肿瘤进展和肿瘤免疫中的作用仍不清楚:在这项研究中,我们基于基因型组织表达(GTEx)、癌症基因组图谱(TCGA)、癌症细胞系百科全书(CCLE)和肿瘤免疫共生小鼠(TISMO)等数据集,对 33 种不同癌症中的 CMPK2 进行了系统分析。我们的研究重点包括 CMPK2 表达模式的临床意义、潜在调控机制及其与肿瘤免疫特征的关系,包括对免疫检查点抑制剂治疗的反应性。23种癌症的CMPK2表达升高,2种癌症的CMPK2表达降低。接收者操作特征曲线分析表明,CMPK2的表达对16种癌症具有较高的诊断价值。卡普兰-梅耶生存分析表明,CMPK2高表达与肾皮肤色素细胞癌(KICH)、子宫体子宫内膜癌(UCEC)和葡萄膜黑色素瘤(UVM)的总生存期(OS)、疾病特异性生存期(DSS)和无进展间期(PFI)较低有关,而与皮肤皮肤黑色素瘤(SKCM)则相反。免疫微环境相关分析表明,在各种肿瘤中,CMPK2的表达与免疫细胞浸润以及免疫检查点的表达之间存在密切联系:结果:值得注意的是,在四个小鼠免疫疗法队列中,CMPK2在治疗后小鼠肿瘤中的表达。在五个临床免疫疗法队列中,CMPK2高表达的患者对免疫疗法的反应更好。此外,CMPK2 基因的甲基化水平与其表达和肿瘤预后密切相关。在这些癌症中,SKCM的临床和免疫学指标与CMPK2的表达密切相关:我们的分析初步描述了 CMPK2 在癌症进展和免疫微环境中的复杂功能,凸显了其作为免疫疗法诊断和治疗靶点的潜力。
Comprehensive Pan-cancer Analysis of CMPK2 as Biomarker and Prognostic Indicator for Immunotherapy.
Background: UMP-CMP kinase 2 (CMPK2) is involved in mitochondrial DNA synthesis, which can be oxidized and released into the cytoplasm in innate immunity. It initiates the assembly of NLRP3 inflammasomes and mediates various pathological processes such as human immunodeficiency virus infection and systemic lupus erythematosus. However, the role of CMPK2 in tumor progression and tumor immunity remains unclear.
Methods: We identified CMPK2 expression patterns in the Genotype Tissue-Expression (GTEx), The Cancer Genome Atlas (TCGA), and the Cancer Cell Line Encyclopedia (CCLE) databases. Validation was performed using immunohistochemical staining data from the Human Protein Atlas (HPA) database and qPCR experiments. Receiver operating characteristic curve analysis and Kaplan-Meier survival analysis were conducted to assess the clinical relevance of CMPK2 expression. The Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data (ESTIMATE) algorithm and the Tumor IMmune Estimation Resource (TIMER) database were used to evaluate the correlation between CMPK2 and immune infiltration in tumors. The Tumor Immune Syngeneic Mouse (TISMO) database and other public datasets were utilized to assess the impact of CMPK2 on immune therapy response. MEXPRESS and MethSurv databases were employed to investigate the effects of methylation on CMPK2 expression.
Results: CMPK2 expression was elevated in 23 cancers and decreased in two cancers. Furthermore, CMPK2 expression had a high diagnostic value for 16 cancers. Elevated CMPK2 expression was associated with lower overall survival (OS), disease-specific survival (DSS), and progression- free interval (PFI) in four cancers. Immune microenvironment-related analysis revealed strong associations between CMPK2 expression and immune cell infiltration, as well as immune checkpoint expression across various tumors. Notably, in four mouse immunotherapy cohorts, CMPK2 expression in treated mouse tumors was higher post-treatment. In five clinical immunotherapy cohorts, patients with high CMPK2 expression show better responses to immunotherapy. Moreover, the methylation level of CMPK2 gene was closely correlated to its expression and tumor prognosis. Among these cancers, the clinical and immunological indications of skin cutaneous melanoma (SKCM) are particularly closely related to CMPK2 expression.
Conclusion: Our analysis preliminarily describes the complex function of CMPK2 in cancer progression and immune microenvironment, highlighting its potential as a diagnostic and therapeutic target for immunotherapy.
期刊介绍:
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes.
Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.