CDCA5对肝癌患者预后的影响及机制研究

The effect of CDCA5 on the prognosis and growth promoting in hepatocellular carcinoma

目的探讨细胞分裂周期相关蛋白5(CDCA5)对肝癌患者临床预后的影响,并探讨其在肝癌发生、发展过程中的作用机制。方法收集2009年9月~2012年9月在南充市中心医院肝胆外科行根治性肝癌切除术的178例患者临床病理资料,免疫组化检测CDCA5在肝癌组织和正常肝脏组织中的表达,分析CDCA5与患者临床病理及预后的关系。构建质粒,敲低及过表达CDCA5。MTT法测定不同表达CDCA5对肝癌细胞增殖的影响,流式细胞术检测细胞周期的变化。将普通HepG2细胞组,CDCA5低表达组的细胞分别注射于裸鼠成瘤,观察成瘤时间。第30天处死小鼠,观察瘤体状态。免疫组化检测CDCA5在裸鼠肿瘤中的表达。结果 CDCA5在肝癌组织中表达量较正常肝脏组织明显增高(P<0.05)。CDCA5高表达患者肿瘤直径较大,微血管侵犯发生率高,且患者无瘤生存率及总生存率较CDCD5低表达患者差(P<0.05)。CDCA5促进了肝癌细胞增殖,敲低CDCA5后,肝癌HepG2细胞生长阻滞在G2期。30天后,两组裸鼠瘤体重量比较差异有统计学意义(P<0.05)。结论 CDCA5对肝癌患者的预后可能有一定预测作用;其能显著促进肝癌细胞的增殖能力,通过调控CDCA5对抑制肝癌细胞的生长有一定意义。

Objective To investigate the impact of CDCA5 on the prognosis for patients with hepatocellular carcinoma(HCC) and explore its growth-promoting effect in hepatoma cells.Methods The clinical and pathological data of 178 patients underwent curative hepatectomy of HCC were analyzed, retrospectively. The expression of CDCA5 in tumor, and normal liver tissues was detected by immunohistochemistry. The impact of CDCA5 on clinicopathology and prognosis was analyzed. Plasmids were constructed to knock down and overexpress of CDCA5. The effect of different expression of CDCA5 on the proliferation of hepG2 cells was analyzed by MTT assay. The changes of cell cycle of hepG2 cells were detected by flow cytometry. Nude mice were injected with CDCA5 low expression and normal expression of HepG2 cells subcutaneously. Mice were sacrificed on the 30 th day for the observation of tumor status. Immunohistochemistry was used to detect CDCA5 expression in tumor tissue of nude mice.Results The expression of CDCA5 in HCC was significantly higher than that in normal liver tissues. Patients with high expression of CDCA5 had larger tumor diameter, high incidence of microvascular invasion, poorer disease-free survival and overall survival than patients with low expression of CDCA5. The results of in vitro experiments suggest that CDCA5 promoted the proliferation of liver cancer cells. HepG2 cells growth were arrested in G2 phase after knocking down CDCA5. The tumor weights were 0.89±0.07 and 0.66±0.11 in control group and CDCA5 knock down group, respectively(P<0.05).Conclusion CDCA5 can significantly promote the proliferation of hepatocellular carcinoma. CDCA5 may become the target of hepatocellular carcinoma.