Decoding the Role of CDCA Genes in Breast Cancer Progression: Insights From in Silico and Functional Assay

IF 1.6 4区医学 Q4 ONCOLOGY

Asia-Pacific journal of clinical oncology Pub Date : 2025-04-17 DOI:10.1111/ajco.14173

Yongsheng Zhao, Xiaocha Ma, Jun Zhou

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引用次数: 0

Abstract

Background

The cell division cycle-associated (CDCA) genes regulate key cellular processes like cell cycle progression and division. This study evaluates the diagnostic and clinical relevance of CDCA genes in breast cancer.

Methodology

Breast cancer and normal breast cell lines were cultured and analyzed for CDCA gene expression using RT-qPCR and further validated using public databases. Functional assays, including cell proliferation, colony formation, and wound healing, were performed following siRNA-mediated knockdown of CDCA2 and CDCA3. Mutational, CNV, methylation, and survival analyses, along with miRNA regulation and PPI network construction, were conducted to explore the role of CDCA genes in breast cancer progression.

Results

Our findings revealed significant upregulation of CDCA genes in breast cancer cell lines compared to normal controls, with all these genes exhibiting the highest diagnostic potential based on AUC values in ROC analysis. Pathological stage analysis indicated that CDCA5 and CDCA7 expression significantly varied across different breast cancer stages. Mutational analysis showed that CDCA2 had the highest mutation rate, with missense mutations being the most common. CNV analysis revealed amplification events in several CDCA genes, particularly CDCA2, CDCA3, CDCA4, and CDCA7. Promoter methylation analysis revealed significant hypomethylation in the CDCA genes in breast cancer, which correlated negatively with their expression. Survival analysis demonstrated that high expression of CDCA2, CDCA3, CDCA4, CDCA5, CDCA7, and CDCA8 was associated with worse overall survival, highlighting their prognostic significance. Furthermore, immune infiltration analysis revealed significant correlations between CDCA gene expression and immune cell types, suggesting a role in immune modulation. miRNA analysis identified specific miRNAs targeting CDCA genes, with several showing potential as diagnostic biomarkers. Lastly, the knockdown of CDCA2 and CDCA3 in breast cancer cells significantly reduced cell proliferation, colony formation, and migration, indicating their critical roles in tumor growth and metastasis.

Conclusion

This study highlights CDCA genes as promising diagnostic and prognostic biomarkers in breast cancer. Their upregulation correlates with poor survival, and the knockdown of CDCA2 and CDCA3 impairs tumor growth, emphasizing their potential as therapeutic targets. These findings suggest that CDCA genes could be integrated into clinical practice for improved breast cancer management.

Clinical trial number

Not applicable.

Abstract Image

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解码CDCA基因在乳腺癌进展中的作用：来自计算机和功能分析的见解。

背景：细胞分裂周期相关（CDCA）基因调控细胞周期进程和分裂等关键细胞过程。本研究评估CDCA基因在乳腺癌中的诊断和临床意义。方法：培养乳腺癌和正常乳腺细胞系，采用RT-qPCR分析CDCA基因表达，并利用公共数据库进一步验证。在sirna介导的CDCA2和CDCA3敲低后，进行功能分析，包括细胞增殖、集落形成和伤口愈合。通过突变、CNV、甲基化和生存分析，以及miRNA调控和PPI网络构建，探讨CDCA基因在乳腺癌进展中的作用。结果：我们的研究结果显示，与正常对照相比，CDCA基因在乳腺癌细胞系中显著上调，根据ROC分析的AUC值，所有这些基因都显示出最高的诊断潜力。病理分期分析表明，CDCA5和CDCA7在不同乳腺癌分期中的表达差异显著。突变分析表明，CDCA2的突变率最高，错义突变最为常见。CNV分析揭示了几个CDCA基因的扩增事件，特别是CDCA2， CDCA3， CDCA4和CDCA7。启动子甲基化分析显示，乳腺癌中CDCA基因显著的低甲基化，与CDCA基因的表达呈负相关。生存分析显示，CDCA2、CDCA3、CDCA4、CDCA5、CDCA7和CDCA8的高表达与较差的总生存相关，突出了它们的预后意义。此外，免疫浸润分析显示CDCA基因表达与免疫细胞类型之间存在显著相关性，提示其在免疫调节中起作用。miRNA分析确定了靶向CDCA基因的特异性miRNA，其中一些显示出作为诊断性生物标志物的潜力。最后，在乳腺癌细胞中敲低CDCA2和CDCA3可显著降低细胞增殖、集落形成和迁移，表明它们在肿瘤生长和转移中起关键作用。结论：本研究强调CDCA基因是乳腺癌诊断和预后的有希望的生物标志物。它们的上调与低生存率相关，CDCA2和CDCA3的下调会损害肿瘤生长，强调它们作为治疗靶点的潜力。这些发现表明，CDCA基因可以整合到临床实践中，以改善乳腺癌的管理。临床试验号：不适用。

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

Asia-Pacific journal of clinical oncology 医学-肿瘤学

CiteScore

3.40

自引率

0.00%

发文量

175

审稿时长

6-12 weeks

期刊介绍： Asia–Pacific Journal of Clinical Oncology is a multidisciplinary journal of oncology that aims to be a forum for facilitating collaboration and exchanging information on what is happening in different countries of the Asia–Pacific region in relation to cancer treatment and care. The Journal is ideally positioned to receive publications that deal with diversity in cancer behavior, management and outcome related to ethnic, cultural, economic and other differences between populations. In addition to original articles, the Journal publishes reviews, editorials, letters to the Editor and short communications. Case reports are generally not considered for publication, only exceptional papers in which Editors find extraordinary oncological value may be considered for review. The Journal encourages clinical studies, particularly prospectively designed clinical trials.