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DAZAP2在乳腺癌中的表达及其生物学功能OA

Expression of DAZAP2 in breast cancer and its biological function

中文摘要英文摘要

目的 探讨无精子症缺失基因相关蛋白2(DAZAP2)在乳腺癌中的表达及其对肿瘤生物学行为的影响.方法 通过TCGA数据库分析DAZAP2的表达水平与患者生存之间的关系.采用免疫组化方法检测DAZAP2在乳腺癌和癌旁组织中的表达水平并分析其与临床病理特征的关系,使用Kaplan-Meier对不同DAZAP2表达水平患者的总生存期(OS)及无复发生存期(RFS)进行分析.分别构建敲低和过表达DAZAP2的乳腺癌稳转细胞系,通过CCK-8与克隆形成实验评估乳腺癌细胞增殖能力的变化,通过细胞划痕和Transwell实验评估乳腺癌细胞迁移和侵袭能力的变化.结果 生物信息学分析和免疫组化结果显示,DAZAP2在乳腺癌组织中的表达水平低于癌旁组织(P<0.001),且其蛋白表达水平与患者的组织学分级和淋巴结转移呈负相关(P<0.05).Kaplan-Meier生存分析结果显示,DAZAP2低表达与乳腺癌患者不良预后相关(P<0.05).CCK-8实验显示,与sh-Ctrl组 相 比,sh-DAZAP2-1组和sh-DAZAP2-2组乳腺癌细胞增殖活性升高(F=52.38,P<0.001);与Flag组 相 比,Flag-DAZAP2组细胞增殖活性降低(F=41.67,P<0.001).克隆形成实验显示,与sh-Ctrl组相比,sh-DAZAP2-1组和sh-DAZAP2-2组克隆形成数增加(F=12.74,P<0.01);与Flag组相比,Flag-DAZAP2组克隆形成数减少(t=9.86,P<0.001).细胞划痕实验显示,与sh-Ctrl组相比,sh-DAZAP2-1组和sh-DAZAP2-2组划痕愈合率升高(F=18.23,P<0.01);与Flag组相比,Flag-DAZAP2组划痕愈合率降低(t=10.42,P<0.001).Transwell实验显示,与sh-Ctrl组相比,sh-DAZAP2-1组和sh-DAZAP2-2组细胞迁移及侵袭数量均增加(F=55.16、68.42,均P<0.001);与Flag组相比,Flag-DAZAP2组细胞迁移及侵袭数量均减少(t=6.18、5.73,均P<0.01).结论 DAZAP2高表达可通过抑制乳腺癌细胞的增殖、迁移及侵袭能力,延缓乳腺癌细胞的恶性进展.

Objective To investigate the expression of DAZ associated protein 2(DAZAP2)in breast cancer and its effect on the biological behavior of tumor cells.Methods The relationship between DAZAP2 expression and pa-tient survival was analyzed using data from The Cancer Genome Atlas(TCGA)database.Immunohistochemistry(IHC)was performed to detect DAZAP2 expression in breast cancer tissues and paratumoral tissues,and its corre-lation with clinicopathological characteristics was evaluated.Kaplan-Meier analysis was used to assess overall sur-vival(OS)and recurrence-free survival(RFS)of patients with different DAZAP2 expression levels.Stable breast cancer cell lines with DAZAP2 knockdown or overexpression were established.The proliferation ability of breast cancer cells was evaluated by CCK-8 and colony formation assays,while migration and invasion abilities were de-tected by wound healing and Transwell assays.Results Bioinformatics analysis and IHC results showed that DAZAP2 expression was significantly lower in breast cancer tissues than in paratumoral tissue(P<0.001).More-over,DAZAP2 protein expression was negatively correlated with histological grade and lymph node metastasis(P<0.05 for both).Kaplan-Meier survival analysis revealed that low DAZAP2 expression was associated with poor prognosis in breast cancer patients(P<0.05).The CCK-8 assay showed that,compared with the sh-Ctrl group,the proliferative activity of breast cancer cells significantly increased in the sh-DAZAP2-1 and sh-DAZAP2-2 groups(F=52.38,P<0.001),whereas compared with the Flag group,cell proliferative activity significantly de-creased in the Flag-DAZAP2 group(F=41.67,P<0.001).The colony formation assay demonstrated that,com-pared with the sh-Ctrl group,the number of colonies significantly increased in the sh-DAZAP2-1 and sh-DAZAP2-2 groups(F=12.74,P<0.01),whereas compared with the Flag group,the number of colonies was significantly re-duced in the Flag-DAZAP2 group(t=9.86,P<0.001).The wound-healing assay showed that,compared with the sh-Ctrl group,the wound closure rates significantly increased in the sh-DAZAP2-1 and sh-DAZAP2-2 groups(F=18.23,P<0.01),whereas compared with the Flag group,the wound closure rate significantly decreased in the Flag-DAZAP2 group(t=10.42,P<0.001).The Transwell assays showed that,compared with the sh-Ctrl group,the numbers of migrated and invaded cells significantly increased in the sh-DAZAP2-1 and sh-DAZAP2-2 groups(F=55.16 and 68.42,respectively;both P<0.001),whereas compared with the Flag group,the numbers of mi-grated and invaded cells significantly decreased in the Flag-DAZAP2 group(t=6.18 and 5.73,respectively;both P<0.01).Conclusion High DAZAP2 expression can delay the malignant progression of breast cancer by sup-pressing the proliferation,migration,and invasion of breast cancer cells.

徐道军;王子明;吴正升

安徽医科大学基础医学院病理学教研室,合肥 230032||安徽医科大学第三附属医院 病理科,合肥 230061安徽医科大学第三附属医院 肿瘤科,合肥 230061安徽医科大学基础医学院病理学教研室,合肥 230032||安徽医科大学第一附属医院病理科,合肥 230022

医药卫生

DAZAP2乳腺癌增殖侵袭迁移

DAZAP2breast cancerproliferationinvasionmigration

《安徽医科大学学报》 2026 (9)

1513-1521,9

国家自然科学基金项目(编号:82473059) National Natural Science Foundation of China(No.82473059)

10.19405/j.cnki.issn1000-1492.2026.09.002

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