血清DKK1水平对肝细胞癌(HCC)患者预后判断的临床价值

Prognostic significance of serum DKK1 in hepatocellular carcinoma (HCC) patients

目的评估血清Dickkopf-l（DKKl）水平与肝细胞癌（hepatocellular carcinoma，HCC）患者术后复发转移和预后的相关性。方法收集2011至2012年间72例在复旦大学附属中山医院进行HCC根治切除患者的术前血清以及其中43例术后1个月的血清，随访至2013年10月。采用ELISA方法定量检测HCC患者术前以及术后血清DKKl水平，分析DKKl高、低组患者主要临床相关资料差异，并评价其与患者复发、预后的相关性。结果1年内共有21人发生复发，1年复发率为26．92％。高DKKl组1年无瘤生存率显著低于低DKKl组（50.0％vs．77．8％，P=0．011）。复发低危亚组中高DKKl组复发率高于低DKKl组患者，包括单个肿瘤（73．3％佻．14．0％，P=0．037）、无卫星灶（56．3％vs．14．3％，P=0．034）、无血管侵犯（37．5％叫．12．5％，P：0．002）、BCLC0＋A（53．3％w．15．2％，P：0．010）。两组患者的临床病理特征的差异无统计学意义。多因素结果提示高DKKl为术后无瘤生存的独立预后因素（HR为3．753，95％CI为1．495-9．424，P=0．005）。受试者工作特征曲线分析显示术前血清DKKl水平对预测HCC患者术后复发具有较好的特异性（82．35％）。术后DKKl持续维持在高水平的患者具有更高的复发率（50．0（）％）。结论术前血清高水平DKKl预示HCC患者早期复发率高。血清DKKl水平可有效预测HCC切除术后患者的预后，监测DKKl可以帮助临床制定最有效的HCC治疗方案。

Objective To invesigate the prognostic values of serum Dickkopf-1 （DKK1）in hepatocellular carcinoma （HCC） patients after curative resection. Methods Preoperative sera samples were collected from 72 selective HCC patients undergoing curative resection during 2011 and 2012 in Zhongshan hospital. Moreover,postoperative sera of 43 patients who enrolled in present study were collected one month after resection. Follow-up was ended on Oct. ,2013. ELISA was used to detect the concentrations of preoperative and postoperative DKK1 in serum from the patients. Clinical-pathological features were compared between high and low DKK1 level patients to evaluate the correlation between DKK1 and recurrence of HCC. Results During the follow-up,21 of 78 enrolled patients suffered recurrence and the 1-year recurrence rates was 26. 92%. High DKK1 expression group had lower /-year time to progress （TTP） rates compared with low DKK1 expression group （50.0 % vs. 77.8 %, P = 0.011）. Patients with preoperative high DKK1 expression showed a relatively higher risk of developing postoperative recurrence than those with low DKK1 expression in low recurrence risk subgroups, including single tumor （73.3% vs. 14. 0 %//00, P = 0. 037）, absence of satellite lesions （56.3 % vs. 14.3 %, P = 0. 034）, absence of vascular invasion （37. 5 % vs. 12.5 %, P = 0.002） and BCLC stage 0 ＋ A （53. 3%vs. 15. 2%, P = 0. 01（））. No significant clinicopathlolgical characteristics was found between the two groups. Multivariate analysis revealed that DKKl was an independent prognostic factor for TrIP （ HR： 3. 753,95% CI： 1. 495 - 9. 424, P = 0. 005）. Receiver operating characteristics curve analysis showed that preoperative DKK1 had high specificity （82.35%） in predicting recurrence after resection. Patients who remained high DKK1 levels after resection had highest recurrence probabilities （50.00%. Conclusions High level of preoperative serum DKKI was associated with early recurrence of HCC after curative resection. DKK1 is a novel prognostic predictor for HCC patients and monitoring DKK1 could help tailing the most effective antitumor strategies.