Exploring MAP3K genes in gastric cancer: biomarkers, tumor microenvironment dynamics, and chemotherapy resistance.

IF 2.7 3区生物学

Hereditas Pub Date : 2025-02-03 DOI:10.1186/s41065-025-00364-0

Senhui Wei, Ying Li, Jing Zhou, Yongming Xia

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引用次数: 0

Abstract

Background: Gastric cancer (GC) presents a significant global health burden, necessitating a deeper understanding of its molecular underpinnings for improved diagnostics and therapeutics.

Methods: In this study, we investigated the expression profiles and clinical implications of MAP3K genes in GC using in silico and in vitro experiments.

Results: Utilizing RT-qPCR analysis, we observed significant up-regulation of MAP3K1, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 in GC cell lines, while MAP3K2, MAP3K3, MAP3K11, MAP3K12, MAP3K13, MAP3K14, and MAP3K15 exhibited down-regulation. Prognostic evaluation revealed that elevated expression of MAP3K1, MAP3K4, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 was associated with shorter overall survival (OS), emphasizing their clinical significance. Furthermore, the diagnostic potential was demonstrated through robust Receiver operating characteristics (ROC) curve analysis, indicating the strong discriminatory power of these genes in distinguishing GC patients. Proteomic analysis further confirmed the higher expression of MAP3K1, MAP3K4, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 genes in GC. Methylation profiling further supported the idea that promoter hypomethylation of MAP3K1, MAP3K4, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 genes was associated with their up-regulation. Single-cell functional analysis elucidated the involvement of MAP3K genes in shaping the tumor microenvironment. miRNA-mRNA network analysis revealed intricate regulatory mechanisms, with hsa-mir-200b-3p emerging as a key regulator. Finally, the MAP3K1 knockdown has shown significant impacts on the cellular behavior of the BGC823 cells.

Conclusion: This comprehensive assessment provides valuable insights into the role of MAP3K genes in GC, offering avenues for further research and therapeutic exploration.

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探索胃癌中的MAP3K基因：生物标志物、肿瘤微环境动力学和化疗耐药。

背景：胃癌（GC）是一个重大的全球健康负担，需要更深入地了解其分子基础，以改进诊断和治疗。方法：本研究通过计算机和体外实验研究MAP3K基因在胃癌中的表达谱及其临床意义。结果：通过RT-qPCR分析，我们观察到GC细胞株中MAP3K1、MAP3K4、MAP3K5、MAP3K6、MAP3K7、MAP3K8、MAP3K9和MAP3K10表达显著上调，而MAP3K2、MAP3K3、MAP3K11、MAP3K12、MAP3K13、MAP3K14和MAP3K15表达下调。预后评估显示，MAP3K1、MAP3K4、MAP3K7、MAP3K8、MAP3K9和MAP3K10的表达升高与总生存期（OS）缩短相关，强调了其临床意义。此外，通过稳健的受试者工作特征（ROC）曲线分析证明了诊断潜力，表明这些基因在区分GC患者方面具有很强的区分能力。蛋白质组学分析进一步证实了MAP3K1、MAP3K4、MAP3K7、MAP3K8、MAP3K9和MAP3K10基因在GC中的高表达。甲基化分析进一步支持了MAP3K1、MAP3K4、MAP3K7、MAP3K8、MAP3K9和MAP3K10基因的启动子低甲基化与它们的上调相关的观点。单细胞功能分析阐明了MAP3K基因参与塑造肿瘤微环境。miRNA-mRNA网络分析揭示了复杂的调控机制，hsa-mir-200b-3p是一个关键的调控因子。最后，MAP3K1敲低对BGC823细胞的细胞行为有显著影响。结论：这项综合评估为MAP3K基因在胃癌中的作用提供了有价值的见解，为进一步的研究和治疗探索提供了途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.