探讨肝细胞癌（肝癌）患者中细胞分裂周期蛋白10依赖性转录因子1（CDT1）的表达及其预后预测价值。

回顾性分析2014年1月至2016年1月在中国人民解放军联勤保障部队第九〇〇医院行肝切除术的237例肝癌患者临床资料（肝癌组），同时选取200例健康志愿者作为对照组。入组人员均签署知情同意书，符合医学伦理学规定。其中肝癌组男149例，女88例；年龄31~82岁，中位年龄51岁。对照组男110例，女90例；年龄30~70岁，中位年龄48岁。采用Western blot检测肝癌和癌旁组织中CDT1蛋白表达情况，荧光原位杂交技术检测肝癌组织中CDT1 mRNA表达，RT-PCR检测血清CDT1 mRNA表达。根据癌组织中CDT1 mRNA相对表达量平均值，将肝癌组分为CDT1高表达组和CDT1低表达组。癌组织CDT1 mRNA表达与HCC患者术前临床病理参数的关系分析采用t检验或单因素方差分析。血清CDT1 mRNA表达与血清AFP的关系分析采用线性相关分析。生存分析采用Kaplan-Meier法和Log-rank检验。肝癌患者术后肿瘤复发转移影响因素分析采用Cox多因素分析。

肝癌组癌组织CDT1 mRNA平均相对表达量为2.20±0.18，明显高于癌旁组织的1.86±0.24（t=16.705，P<0.05）。肝癌组血清CDT1 mRNA相对表达量为1.62±0.18，明显高于对照组的1.34±0.15（t=17.398，P<0.05）。肝癌组癌组织CDT1蛋白表达明显强于癌旁组织。癌组织CDT1 mRNA相对表达量与肝癌患者术前肿瘤直径、肿瘤包膜、术前HBsAg、微血管侵犯、肿瘤分化相关（t=-3.107，-8.352，-2.221，-2.981，3.745；P<0.05）。肝癌术前和再复发时血清CDT1 mRNA相对表达量均与血清AFP成正相关（r=0.507，0.403；P<0.05）。CDT1高表达组和低表达组术后3年复发率分别为35.11%和24.53%，5年生存率分别为56.49%和73.58%，差异有统计学意义（χ²=6.520，5.566；P<0.05）。Cox多因素分析显示，CDT1 mRNA相对表达量≥2.20是患者术后肿瘤复发转移的独立危险因素（HR=1.950，95%CI：1.217~3.124，P<0.05）。

CDT1在肝癌患者中高表达，且与肝癌复发、进展相关，CDT1高表达患者复发率较高，预后较差。

To investigate the expression level and prognostic value of cell division cycle protein 10 dependent transcript 1 (CDT1) in patients with hepatocellular carcinoma (HCC).

Clinical data of 237 HCC patients (HCC group) who underwent hepatectomy in the No.900 Hospital of Joint Logistics Support Force of PLA from January 2014 to January 2016 were retrospectively analyzed, and 200 healthy volunteers were assigned into the control group. The informed consents of all patients were obtained and the local ethical committee approval was received. In the HCC group, 149 patients were male and 88 female, aged from 31 to 82 years, with a median age of 51 years. In the control group, 110 patients were male and 90 female, aged from 30 to 70 years, with a median age of 48 years. The expression level of CDT1 protein in the HCC and adjacent tissues was detected by Western blot. The expression level of CDT1 mRNA in the HCC tissues was determined by fluorescence in situ hybridization. The expression level of CDT1 mRNA in the serum was detected by RT-PCR. According to the average relative expression level of CDT1 mRNA in the HCC tissues, patients in the HCC groups were further divided into the high and low CDT1 expression groups. The relationship between the expression of CDT1 mRNA in the HCC tissues and clinicopathological parameters of HCC patients before operation was assessed by t test or one-way ANOVA. The relationship between serum expression of CDT1 mRNA and serum AFP level was determined by the linear correlation analysis. Survival analysis was conducted by Kaplan-Meier method and Log-rank test. The influencing factors of postoperative recurrence and metastasis of HCC were identified by multivariate Cox regression model.

The average relative expression level of CDT1 mRNA in the HCC tissues was 2.20±0.18, significantly higher than 1.86±0.24 in the adjacent tissues (t=16.705, P<0.05). The relative expression level of serum CDT1 mRNA in the HCC group was 1.62±0.18, significantly higher than 1.34±0.15 in the control group (t=17.398, P<0.05). In the HCC group, the expression level of CDT1 protein in the HCC tissues was significantly higher than that in adjacent tissues. The relative expression level of CDT1 mRNA in the HCC tissues was correlated with preoperative tumor diameter, tumor encapsulation, preoperative HBsAg, microvascular invasion and tumor differentiation of patients with HCC (t=-3.107, -8.352, -2.221, -2.981, 3.745; P<0.05). The relative expression of serum CDT1 mRNA before surgery and after recurrence of HCC was positively correlated with serum AFP level (r=0.507, 0.403; P<0.05). The 3-year recurrence rates were 35.11% and 24.53% in the high and low CDT1 expression groups, and the 5-year survival rates were 56.49% and 73.58%, respectively, where significant difference was observed (χ²=6.520, 5.566; P<0.05). Multivariate Cox regression analysis showed that the relative expression level of CDT1 mRNA≥2.20 was an independent risk factor for the postoperative HCC recurrence and metastasis (HR=1.950, 95%CI: 1.217-3.124, P<0.05).

CDT1 is highly expressed in HCC patients. It is associated with the recurrence and progression of HCC. High recurrence rate and poor prognosis are observed in patients with high expression of CDT1.