CDC20、TOP2A、NEK2的表达与食管鳞状细胞癌分期和预后的相关性及其对肿瘤细胞增殖和转移的影响

Correlation analysis of CDC20, TOP2A, and NEK2 gene expression with esophageal squamous cell carcinoma stage and survival prognosis, and their effect on tumor cell proliferation and metastasis function

目的:系统分析食管鳞状细胞癌(ESCC)中细胞分裂周期20同源物(CDC20)、拓扑异构酶Ⅱα(TOP2A)、非有丝分裂相关激酶2(NEK2)基因表达与分期和预后的关系,探讨三者对ESCC细胞的增殖和转移能力的影响,旨在寻找理想的生物标志物和治疗靶点。方法 :收集112例ESCC患者的临床资料和组织。利用实时荧光定量PCR、蛋白免疫印迹和免疫组织化学法分析CDC20、TOP2A、NEK2基因的表达差异;通过随访对患者进行生存分析;培养ESCC细胞系,对细胞分别转染过表达CDC20、TOP2A、NEK2的重组载体pcCDC20、pcTOP2A、pcNEK2,CCK-8实验和伤口愈合实验分析ESCC的增殖率和迁移率变化。结果 :与癌旁非癌组织比,ESCC组中CDC20、TOP2A、NEK2的mRNA和蛋白水平均增高。CDC20、TOP2A的高表达与淋巴结转移和生存预后差相关;NEK2的高表达与肿瘤组织大小相关。分别与各组阴性对照组比较,pcCDC20、pcTOP2A、pcNEK2组的细胞增殖率和迁移率均升高。结论:CDC20、TOP2A、NEK2在ESCC组织中表达上调,三者都与ESCC的不良预后相关;CDC20、TOP2A、NEK2均促进ESCC细胞的增殖和迁移。CDC20、TOP2A、NEK2基因均可能是ESCC的潜在诊断和预后生物标志物。

Objective : To systematically analyze the relationship between CDC20, TOP2A, and NEK2 gene expression and stage and prognosis in esophageal squamous cell carcinoma(ESCC), discuss the effect of the three on the proliferation and metastatic ability of ESCC cells, and seek to find ideal biomarkers and therapeutic targets.Method : The clinical data and organization of 112 patients with ESCC were collected. Real-time fluorescent quantitative PCR, Western blotting, and immunohistochemistry were used to analyze the expression differences of CDC20, TOP2A, NEK2 genes. Survival and prognosis analysis of the ESCC patients was carried out through followup;ESCC cell lines were cultured, the cells were transfected with recombinant vectors pcCDC20, pcTOP2A, and pcNEK2 overexpressing CDC20, TOP2A, and NEK2, respectively, and the proliferation rate and migration of ESCC were analyzed by CCK-8 assay and wound healing assay. Results : Compared with non-cancerous tissues adjacent to cancer, the mRNA and protein levels of CDC20, TOP2A, and NEK2 in the ESCC group increased.The high expression of CDC20 and TOP2A was associated with lymph node metastasis and poor survival prognosis.The high expression of NEK2 was related to the size of tumor tissue. Finally, compared with the negative control group of each group, the cell proliferation rate and migration rate of the pcCDC20, pcTOP2A, and pcNEK2 groups increased. Conclusion : CDC20, TOP2A and NEK2 are up-regulated in ESCC tissues, and all three are associated with poor survival of ESCC. CDC20, TOP2A, and NEK2 promote the proliferation and migration of ESCC cells.CDC20, TOP2A and NEK2 genes may be potential biomarkers for diagnosis and prognosis of ESCC.