多组学分析显示TAOK1可作为多种肿瘤的预后标志物和靶点,尤其是宫颈癌。

IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
OncoTargets and therapy Pub Date : 2025-03-14 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S506582
Li Ning, Xiu Li, Yating Xu, Yu Si, Hongting Zhao, Qingling Ren
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引用次数: 0

摘要

背景:TAOK1是MAPK激酶家族的一员,在微管动力学、DNA损伤反应和神经发育等过程中起着至关重要的作用。虽然TAOK1与肿瘤发生有关,但其在癌症中的致癌作用尚不清楚。本研究旨在探讨TAOK1在多种癌症中的表达、预后和免疫功能之间的关系。方法:利用TCGA、GEO、CCLE等生物信息学数据库分析TAOK1在多种肿瘤中的表达。采用ESTIMATE算法评估TAOK1表达与免疫细胞浸润的相关性。我们还研究了与肿瘤干性、DNA甲基化、基因拷贝数改变和药物敏感性的关系。在体外SiHa和A2780细胞以及体内SiHa细胞中TAOK1过表达的情况下,进一步评估TAOK1的致癌作用。结果:TAOK1是多种癌症的关键预后生物标志物,其高表达与不良预后相关。与免疫细胞浸润、免疫检查点呈显著负相关。GSEA发现其参与关键的肿瘤通路,强调了抑制TAOK1基因的治疗潜力。TAOK1的高表达与DNA甲基化和基因拷贝数变异有关,此外其上游调控因子EP300与TAOK1的表达密切相关。体外细胞实验表明,抑制TAOK1可降低SiHa和A2780细胞的增殖,而过表达TAOK1可促进SiHa细胞的生长。这些发现通过裸鼠致瘤性实验和人体组织免疫组织化学进一步验证。结论:TAOK1是一种有前景的预后生物标志物和潜在的治疗靶点,特别是在宫颈癌中。这些结果支持其在癌症预后和治疗策略方面的临床潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multi-Omics Analysis Revealed That TAOK1 Can Be Used as a Prognostic Marker and Target in a Variety of Tumors, Especially in Cervical Cancer.

Background: Thousand and One Kinase 1 (TAOK1), a member of the MAPK kinase family, plays a crucial role in processes like microtubule dynamics, DNA damage response, and neurodevelopment. While TAOK1 is linked to tumorigenesis, its oncogenic role across cancers remains unclear. This study aims to explore the relationship between TAOK1 expression, prognosis, and immune function in various cancers.

Methods: We analyzed TAOK1 expression in multiple cancers using TCGA, GEO, CCLE, and other bioinformatics databases. The correlation between TAOK1 expression and immune cell infiltration was assessed with the ESTIMATE algorithm. We also examined associations with tumor stemness, DNA methylation, gene copy number alterations, and drug sensitivity. The oncogenic role of TAOK1 was further evaluated in vitro with SiHa and A2780 cells and in vivo with TAOK1 overexpression in SiHa cells.

Results: TAOK1 is a key prognostic biomarker in various cancers and its high expression is associated with poor prognosis. It showed a significant negative correlation with immune cell infiltration and immune checkpoints. GSEA identified its involvement in key tumour pathways, highlighting the therapeutic potential of inhibiting the TAOK1 gene. The high expression of TAOK1 is associated with DNA methylation and gene copy number variation, and in addition its upstream regulator, EP300, is closely associated with TAOK1 expression. In vitro cellular experiments demonstrated that inhibition of TAOK1 reduced the proliferation of SiHa and A2780 cells, whereas overexpression of TAOK1 in SiHa cells promoted growth. These findings were further validated in vivo by nude mouse tumourigenicity assay and human tissue immunohistochemistry.

Conclusion: TAOK1 serves as a promising prognostic biomarker and potential therapeutic target, especially for cervical cancer. These results support its clinical potential in cancer prognosis and treatment strategies.

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来源期刊
OncoTargets and therapy
OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY
CiteScore
9.70
自引率
0.00%
发文量
221
审稿时长
1 months
期刊介绍: OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.
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