Functional Analysis and Experimental Validation of the Prognostic and Immune Effects of the Oncogenic Protein CDC45 in Breast Cancer.

IF 3.3 4区 医学 Q2 ONCOLOGY Breast Cancer : Targets and Therapy Pub Date : 2025-01-09 eCollection Date: 2025-01-01 DOI:10.2147/BCTT.S497975
Jia-Ning Zhang, Lin-Wei Li, Man-Qing Cao, Xin Liu, Zi-Lu Yi, Sha-Sha Liu, Hong Liu
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Abstract

Purpose: Cell division cycle protein 45 (CDC45) plays a crucial role in DNA replication. This study investigates its role in breast cancer (BC) and its impact on tumor progression.

Methods: We utilized the GEO database to screen differentially expressed genes (DEGs) and conducted enrichment analysis on these genes. We established a Nomogram model based on CDC45 and other clinical indicators. Additionally, we performed protein-protein interaction (PPI) network construction, drug sensitivity analysis, and immune correlation analysis of CDC45. The function of CDC45 was further verified through cell and animal experiments.

Results: CDC45 is highly expressed in most tumors, including BC. The expression level of CDC45 was significantly associated with age, sex, race, cancer stage, and molecular subtypes (all p < 0.05). CDC45 was incorporated into a Nomogram model, which showed moderate accuracy in predicting patient prognosis. We also analyzed the co-expression genes of CDC45, including TOPBP1, GINS2, MCM5, GINS1, GINS4, POLE2, MCM2, MCM6, MCM4, and MCM7. Furthermore, CDC45 expression was closely linked to immune infiltration levels, immune checkpoint inhibitors, and the therapeutic response to small molecule drugs. Finally, both in vitro and in vivo experiments confirmed the cancer-promoting effect of CDC45 in BC.

Conclusion: The expression level of CDC45 is linked to the prognosis, immune infiltration, and drug sensitivity of BC. In vitro and in vivo experiments have confirmed that CDC45 acts as a cancer-promoting protein in breast cancer.

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致癌蛋白CDC45在乳腺癌中预后和免疫作用的功能分析和实验验证。
目的:细胞分裂周期蛋白45 (CDC45)在DNA复制中起着至关重要的作用。本研究探讨其在乳腺癌(BC)中的作用及其对肿瘤进展的影响。方法:利用GEO数据库筛选差异表达基因(differential expression genes, DEGs),并对其进行富集分析。我们基于CDC45等临床指标建立Nomogram模型。此外,我们还进行了蛋白-蛋白相互作用(PPI)网络构建、药物敏感性分析和CDC45的免疫相关性分析。通过细胞和动物实验进一步验证了CDC45的功能。结果:CDC45在大多数肿瘤中高表达,包括BC。CDC45表达水平与年龄、性别、种族、肿瘤分期、分子亚型相关(均p < 0.05)。将CDC45纳入Nomogram模型,该模型预测患者预后的准确度中等。我们还分析了CDC45共表达基因TOPBP1、GINS2、MCM5、GINS1、GINS4、POLE2、MCM2、MCM6、MCM4和MCM7。此外,CDC45的表达与免疫浸润水平、免疫检查点抑制剂和对小分子药物的治疗反应密切相关。最后,体外和体内实验均证实了CDC45在BC中的促癌作用。结论:CDC45的表达水平与BC的预后、免疫浸润及药物敏感性有关。体外和体内实验证实,CDC45在乳腺癌中起促癌蛋白的作用。
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来源期刊
CiteScore
4.10
自引率
0.00%
发文量
40
审稿时长
16 weeks
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