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目的 利用生物信息学探讨依托泊苷诱导蛋白2.4(Etoposide-induced 2.4,EI24)在甲状腺癌(Thyroid cancer, THCA)中的诊断和预后价值并进行功能分析和体外实验验证。方法 利用肿瘤基因组图谱(TCGA)数据库和人类蛋白图谱(HPA)数据库分析EI24在THCA中的表达水平及其与临床特征的关系。采用Kaplan-Meier生存分析、Cox回归分析和受试者工作特征曲线(ROC)评价EI24对THCA的诊断及预后价值。通过基因富集分析(GSEA)探索可能的细胞机制和生物学功能，并利用蛋白互作数据库(STRING)探索EI24的互作蛋白。随后，本研究通过细胞转染、实时荧光定量PCR(RT-qPCR)、Western blot(WB)、CCK-8、克隆形成实验、Transwell实验、Oris细胞迁移实验等探讨EI24不同表达水平对THCA细胞功能的影响。结果 与正常甲状腺组织相比，THCA组织中EI24 mRNA及其蛋白水平均呈高表达，且与THCA患者的总生存期(Overall survival, OS)和无进展间期(Progress free interval, PFI)等均显著相关。ROC曲线分析表明，EI24在THCA中的曲线下面积(AUC)为0.900。较高的EI24 mRNA表达与预后不佳有明显相关关系，且M分期、病理阶段和EI24的表达状态是THCA患者PFI的独立危险因素。京都基因与基因组百科全书(KEGG)和GSEA的分析显示，EI24主要通过肿瘤蛋白p53(TP53)调控细胞周期基因和细胞死亡基因的转录、间质-上皮转化因子(MET)激活蛋白酪氨酸激酶2(PTK2)信号、MET信号等途径在THCA中发挥作用。体外实验证实，EI24高表达促进THCA细胞系的增殖、侵袭和迁移能力。结论 EI24在THCA组织中高表达，与THCA预后不良有关，EI24的过表达能促进THCA细胞的增殖、侵袭和迁移，提示EI24可作为THCA预后和诊断的生物标记物以及治疗潜在靶标。
Abstract：Objective To explore the diagnostic and prognostic value of etoposide-induced 2.4(EI24) in thyroid cancer(THCA) using bioinformatics, and to perform functional analysis and in vitro experimental verification. Methods The expression level of EI24 in THCA and its relationship with clinical characteristics were analyzed using TCGA database and HPA database. Kaplan-Meier survival analysis, Cox regression analysis and ROC curve were used to evaluate the diagnostic and prognostic value of EI24 in THCA. Gene enrichment analysis was used to explore the possible cellular mechanism and biological function of EI24, and the STRING database was used to explore the interaction proteins of EI24. Subsequently, in this study, the effects of different expression levels of EI24 on the function of THCA cells were investigated by cell transfection, RT-qPCR, WB, CCK-8, colony formation assay, Transwell assay and Oris cell migration assay. Results Compared with normal thyroid tissues, the mRNA and protein levels of EI24 in THCA tissues were highly expressed, and were significantly correlated with OS and PFI of THCA patients. ROC curve analysis showed that the AUC of EI24 in thyroid cancer was 0.900. Higher EI24 mRNA expression was associated with poor prognosis, and M stage, pathological stage and the expression status of EI24 were independent risk factors for PFI in THCA patients.KEGG and GSEA analysis showed that EI24 played a role in THCA mainly through TP53 regulating the transcription of cell cycle genes and cell death genes, MET activation of PTK2 signaling, MET signaling and other pathways. In vitro experiments confirmed that EI24 was highly expressed and could promote the proliferation, invasion and migration of THCA cells. Conclusion EI24 is highly expressed in THCA tissues, which is associated with poor prognosis of THCA. The overexpression of EI24 can promote the proliferation, invasion and migration of THCA cells, suggesting that EI24 can be used as a biomarker for prognosis and diagnosis of THCA and a potential therapeutic target.
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基本信息:
中图分类号:R736.1
引用信息:
[1]徐宝国,郭瑞,张跃,等.基于生物信息学和实验验证研究探讨EI24在甲状腺癌诊断和预后中的价值[J].新疆医科大学学报,2025,48(06):735-745.
基金信息:
新疆维吾尔自治区自然科学基金项目(2023D01C96)
2025-06-15
2025-06-15