基于多数据库分析CKAP2L在乳腺癌中的表达、预后及免疫相关性

Multi-Database Analysis of CKAP2L Expression, Prognosis, and Immune-Related Correlations in Breast Cancer

摘要: 目的：探讨细胞骨架相关蛋白2样蛋白(CKAP2L)在乳腺癌中的表达特征、预后价值、潜在功能及其与免疫微环境的关系。方法：整合GEPIA3、UALCAN、Kaplan-Meier Plotter、cBioPortal、TIMER3、Metascape等公共数据库，分析TCGA-BRCA队列中CKAP2L的表达差异、生存预后、共表达富集、遗传变异、免疫浸润、免疫检查点及药物敏感性。结果：CKAP2L在乳腺癌组织中显著高表达，并在Luminal、HER2阳性及多种TNBC亚型中较正常组织升高；CKAP2L高表达与较差的无复发生存期和远处转移无病生存期相关，而与总生存期未见显著相关；CKAP2L共表达基因富集于细胞周期、有丝分裂、染色体分离、纺锤体组装、PLK1/Aurora B通路及DNA损伤应答等过程；cBioPortal分析显示CKAP2L遗传突变频率较低(0.8%)；其表达与抑制性免疫细胞、CD80/CD86/TIGIT/HAVCR2等免疫检查点基因显著正相关。药物分析提示CKAP2L高表达细胞对细胞周期/DNA损伤抑制剂敏感，低表达细胞对PI3K/AKT通路抑制剂更敏感，但该结果未通过多重检验校正。结论：CKAP2L在乳腺癌中显著高表达，并与复发转移风险、细胞周期相关功能及免疫微环境改变相关，可能作为乳腺癌潜在预后相关分子和免疫微环境相关候选分子，但其具体机制仍需进一步验证。

Abstract: Objective: To investigate the expression profile, prognostic value, potential biological functions, and association with the immune microenvironment of cytoskeleton-associated protein 2-like (CKAP2L) in breast cancer. Methods: Multiple public databases including GEPIA3, UALCAN, Kaplan-Meier Plotter, cBioPortal, TIMER3 and Metascape were integrated to analyze the differential expression, survival prognosis, co-expression enrichment, genetic variation, immune infiltration, immune checkpoints and drug sensitivity of CKAP2L in the TCGA-BRCA cohort. Results: CKAP2L was significantly upregulated in breast cancer tissues and showed higher expression in Luminal, HER2-positive, and multiple TNBC subtypes compared with normal tissues. High CKAP2L expression was associated with poorer relapse-free survival and distant metastasis-free survival, whereas no significant association was observed with overall survival. Functional enrichment analysis revealed that CKAP2L co-expressed genes were mainly involved in cell cycle regulation, mitosis, chromosome segregation, spindle assembly, PLK1/Aurora B pathways, and DNA damage response. cBioPortal analysis showed a low frequency of CKAP2L genomic alterations (0.8%). CKAP2L expression was positively correlated with immunosuppressive immune cell infiltration and immune checkpoint-related genes, including CD80, CD86, TIGIT, and HAVCR2. Drug sensitivity analysis suggested that CKAP2L-high expressing cells may be more sensitive to cell cycle and DNA damage response inhibitors, whereas CKAP2L-low expressing cells may be more sensitive to PI3K/AKT pathway inhibitors; however, these findings did not remain significant after multiple-testing correction. Conclusion: CKAP2L is highly expressed in breast cancer and is associated with recurrence and metastasis risk, cell cycle-related functions, and immune microenvironment alterations. CKAP2L may serve as a potential prognostic and immune microenvironment-related candidate biomarker in breast cancer, although further experimental validation is required.