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    CDC7在骨肉瘤中的表达、临床意义及生物学功能

    Expression, clinical significance and biological function of CDC7 in osteosarcoma

      摘要
    • 摘要:
      目的 探讨细胞分裂周期蛋白7（CDC7）在骨肉瘤（OS）组织中的表达、临床意义及其对OS细胞增殖、迁移和侵袭能力的影响。
      方法 使用基因表达综合数据库（GEO）中的mRNA芯片数据分析CDC7在OS组织中的表达情况。采用实时荧光定量PCR（RT-qPCR）验证人成骨细胞（hFOB1.19）和OS细胞（HOS、U-2 OS、MG63）中CDC7 mRNA的表达，免疫组织化学染色检测39例OS组织及8例癌旁正常组织中CDC7蛋白的表达。利用总受试者工作特征（SROC）曲线评价CDC7在OS中的诊断效能。绘制Kaplan-Meier生存曲线，分析CDC7表达对OS患者预后的影响；采用单因素和多因素Cox风险比例回归模型分析OS预后不良的危险因素。使用小干扰RNA（si-CDC7）转染HOS细胞，通过CCK-8、EdU实验检测细胞的增殖能力，Transwell实验检测细胞的迁移和侵袭能力。
      结果 多个GEO数据集表明，CDC7在OS中的表达上调（P＜0.05）。与hFOB1.19细胞比较，HOS、U-2 OS、MG63细胞中CDC7 mRNA表达水平升高（P＜0.05）。与正常组织比较，CDC7蛋白在OS组织中表达上调（P＜0.001）。CDC7对OS具有良好的诊断潜力（AUC=0.73，95% CI：0.69~0.77）。CDC7高表达患者的生存率显著低于低表达患者（P=0.028），CDC7高表达是OS不良预后的独立危险因素（HR=2.471，95% CI：1.056~5.781，P=0.037）。沉默CDC7可显著抑制HOS细胞增殖、迁移和侵袭。
      结论 CDC7在OS中的表达上调，可促进OS细胞增殖、迁移和侵袭，有望作为OS诊断及预后评估的分子标志物。

       

      Abstract:
      Objective To investigate the expression and clinical significance of cell division cycle 7 (CDC7) in osteosarcoma (OS) and its effect on the proliferation, migration and invasion of OS cells.
      Methods The mRNA microarray data from the Gene Expression Omnibus (GEO) database was used to analyze the expression of CDC7 in OS tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to verify the expression of CDC7 mRNA in human osteoblast cell line (hFOB1.19) and OS cell lines (HOS, U-2 OS, MG63). Immunohistochemistry (IHC) was used to detect the expression of CDC7 protein in 39 cases of OS tissues and 8 cases of adjacent normal tissues. The summary receiver operating characteristic (SROC) curve was employed to evaluate the diagnostic efficacy of CDC7 in OS. Kaplan-Meier survival curves were plotted to analyze the impact of CDC7 expression on the prognosis of OS patients. Univariate and multivariate Cox proportional hazards regression models were utilized to analyze risk factors for poor prognosis in OS. CDC7 small interfering RNA (si-CDC7) was used to transfect HOS cells, and cell proliferation was assessed using cell counting kit-8 (CCK-8) and EdU assays, while cell migration and invasion were evaluated using Transwell assays.
      Results Multiple GEO datasets indicated that CDC7 expression was up-regulated in OS (P < 0.05). Compared with hFOB1.19 cells, CDC7 mRNA expression was increased in HOS, U-2 OS and MG63 cells (P < 0.05). CDC7 protein was highly expressed in OS tissues compared with normal tissues (P < 0.001). CDC7 demonstrated good diagnostic potential for OS (AUC=0.73, 95% CI: 0.69-0.77). Patients with high CDC7 expression had a significant lower survival rate than those with low CDC7 expression (P=0.028). High CDC7 expression was an independent risk factor for poor prognosis in OS (HR=2.471, 95% CI: 1.056-5.781, P=0.037). Silencing CDC7 significantly inhibited the proliferation, migration and invasion of HOS cells.
      Conclusion The expression of CDC7 is upregulated in OS, and it promotes the proliferation, migration and invasion of OS cells, which is expected to be a molecular marker for the diagnosis and prognosis of OS.

       

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