Pan-cancer genetic profiles of mitotic DNA integrity checkpoint protein kinases.

IF 1.9 4区 医学 Q3 ONCOLOGY
Cancer Biomarkers Pub Date : 2024-12-01 Epub Date: 2025-02-05 DOI:10.3233/CBM-240119
Ayana Meegol Rasteh, Hengrui Liu, Panpan Wang
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引用次数: 0

Abstract

Background: The mitotic DNA integrity checkpoint signaling pathway is potentially involved in cancers that regulate genomic stability where protein kinases play a pivotal role. 16 total protein kinase genes are involved in this pathway: ATM, BRSK1, CDK1, CDK2, CHEK1, CHEK2, MAP3K20, NEK11, PLK1, PLK2, PLK3, PRKDC, STK33, TAOK1, TAOK2, and TAOK3. This study aims to provide pan-cancer profiles of the protein kinases in mitotic DNA integrity checkpoint signaling gene set for potential prognostic and diagnostic purposes, as well as future potential therapeutic targets for cancer in a clinical setting. Methods: Multi-omic data was acquired for the 16 genes; over 9000 samples of 33 types of cancer were analyzed to create pan-cancer profiles of SNV, CNV, methylation, mRNA expression, pathway crosstalk, and microRNA regulation networks. Results: The SNV profile showed that most of these genes have a high SNV mutation frequency across some cancer types, such as UCEC and SKCM. The CNVs of some of these genes are associated with the survival of UCEC, KIRP, and LGG. BRCA, KIRC, LUAD, and STAD might be affected by the mRNA expression of these genes which might involve regulation of copy number, methylation, and miRNA. In addition, these genes also cross-talk with some known cancer pathways. Conclusion: The protein kinases in mitotic DNA integrity checkpoint signaling may play a role in cancer development and, with adequate research, could potentially be developed as biomarkers for cancer diagnosis and prognosis. However, further efforts are necessary to validate their clinical value for diagnosis and prognosis and to develop practical applications in clinical settings. Nevertheless, these pan-cancer profiles offer a better overall understanding as well as useful information for future reference regarding mitotic DNA integrity checkpoint signaling in cancer.

有丝分裂DNA完整性检查点蛋白激酶的泛癌遗传谱。
背景:有丝分裂DNA完整性检查点信号通路可能参与调节基因组稳定性的癌症,其中蛋白激酶起关键作用。共有16个蛋白激酶基因参与这一途径:ATM、BRSK1、CDK1、CDK2、CHEK1、CHEK2、MAP3K20、NEK11、PLK1、PLK2、PLK3、PRKDC、STK33、TAOK1、TAOK2和TAOK3。本研究旨在提供有丝分裂DNA完整性检查点信号基因中蛋白激酶的泛癌谱,用于潜在的预后和诊断目的,以及未来临床环境中癌症的潜在治疗靶点。方法:对16个基因进行多组学分析;研究人员分析了33种癌症的9000多个样本,建立了SNV、CNV、甲基化、mRNA表达、通路串音和microRNA调控网络的泛癌症图谱。结果:SNV谱显示,这些基因大部分在某些癌症类型(如UCEC和SKCM)中具有较高的SNV突变频率。其中一些基因的CNVs与UCEC、KIRP和LGG的存活有关。BRCA、KIRC、LUAD和STAD可能受这些基因mRNA表达的影响,这些基因表达可能涉及拷贝数、甲基化和miRNA的调控。此外,这些基因还与一些已知的癌症途径相互作用。结论:有丝分裂DNA完整性检查点信号中的蛋白激酶可能在癌症的发生发展中发挥作用,如果研究充分,可能成为癌症诊断和预后的生物标志物。然而,需要进一步的努力来验证其在诊断和预后方面的临床价值,并在临床环境中开发实际应用。尽管如此,这些泛癌症谱提供了更好的整体理解,以及对未来癌症中有丝分裂DNA完整性检查点信号传导的有用信息。
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来源期刊
Cancer Biomarkers
Cancer Biomarkers ONCOLOGY-
CiteScore
5.20
自引率
3.20%
发文量
195
审稿时长
3 months
期刊介绍: Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
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