DOK5 as an oncogenic mediator in gastric cancer: Mechanistic insights through bioinformatics and clinical validation

IF 2.5 4区综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES

Journal of Radiation Research and Applied Sciences Pub Date : 2025-08-25 DOI:10.1016/j.jrras.2025.101896

Kun Tao , Junqin Ge , Zihao Ge , Chungen Xing

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引用次数: 0

Abstract

Objective

Gastric cancer (GC) exhibits metastasis-driven mortality, necessitating novel biomarkers. Although Docking Protein 5 (DOK5), a tyrosine kinase substrate previously implicated in neuronal development and signaling cascades, remains mechanistically uncharacterized in GC.

Methods

DOK5's diagnostic and prognostic potential was evaluated via integrated The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data mining. Utilizing 93 surgically resected specimens (2011–2015 retrospective cohort), we correlated DOK5 immunoreactivity with clinicopathological variables. Gene Set Enrichment Analysis (GSEA) elucidated pathway associations.

Results

DOK5 demonstrated significant tumoral overexpression versus normal mucosa, prognosticating reduced survival. Clinical validations confirmed diagnostic capabilities and TNM-stage associations. GSEA revealed that DOK5 expression positively correlated with epithelial-mesenchymal transition (EMT) and Notch signaling.

Conclusion

DOK5 functions as a tumor-promoting factor in GC carcinogenesis, mechanistically facilitating malignant progression through EMT program activation and Notch signaling pathway engagement. Critically, DOK5 immunohistochemistry may serve as a clinically feasible biomarker to stratify high-risk gastric cancer patients during routine histopathology assessment. This establishes DOK5 as both a prognostic indicator and a therapeutic target in GC therapeutics.

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DOK5作为胃癌的致癌介质：通过生物信息学和临床验证的机制见解

目的胃癌（GC）表现为转移性死亡，需要新的生物标志物。虽然对接蛋白5 （DOK5）是一种酪氨酸激酶底物，先前与神经元发育和信号级联反应有关，但在GC中仍未得到机制表征。方法通过综合肿瘤基因组图谱（TCGA）和基因表达图谱（GEO）数据挖掘评估sdok5的诊断和预后潜力。利用93例手术切除的标本（2011-2015年回顾性队列），我们将DOK5免疫反应性与临床病理变量相关联。基因集富集分析（GSEA）阐明了途径关联。结果与正常粘膜相比，dok5表现出明显的肿瘤过表达，预后生存率降低。临床验证证实了诊断能力和tnm分期的相关性。GSEA显示，DOK5的表达与上皮-间质转化（EMT）和Notch信号传导呈正相关。结论在胃癌发生过程中，dok5作为肿瘤促进因子，通过EMT程序激活和Notch信号通路参与促进恶性进展。至关重要的是，在常规组织病理学评估中，DOK5免疫组织化学可能作为临床可行的生物标志物对高危胃癌患者进行分层。这就确立了DOK5作为胃癌治疗的预后指标和治疗靶点。

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

Journal of Radiation Research and Applied Sciences MULTIDISCIPLINARY SCIENCES-

自引率

5.90%

发文量

130

审稿时长

16 weeks

期刊介绍： Journal of Radiation Research and Applied Sciences provides a high quality medium for the publication of substantial, original and scientific and technological papers on the development and applications of nuclear, radiation and isotopes in biology, medicine, drugs, biochemistry, microbiology, agriculture, entomology, food technology, chemistry, physics, solid states, engineering, environmental and applied sciences.