结合炎性细胞因子构建原发性肝癌术后复发的Nomogram模型

目的收集临床指标及相关炎性细胞因子数据,构建肝细胞癌(HCC)术后复发的Nomogram模型。方法选取2014年1月~2016年1月在武汉中心医院行首次行肝切除术治疗的314例HCC患者,根据随访结果分为无复发组与复发组。收集患者一般资料,检测肝功能及炎性细胞因子水平。计数资料2组间比较采用χ^2检验,等级资料2组间比较采用Mann-Whitney U检验。采用受试者工作特征曲线(ROC曲线)获得计量资料的最佳截断值。复发的独立危险因素采用多因素Cox比例风险模型分析;根据多因素Cox比例风险模型的结果构建Nomogram模型,进行内部数据验证并计算一致性指数(C-index)。结果术后随访1~40个月,中位随访期13个月,无复发患者140例,复发患者174例,中位无复发生存期为19个月,半年无复发生存率68. 2%,1年无复发生存率57. 3%,2年无复发生存率45. 9%。复发组患者的年龄、肿瘤最大直径、BMI、IL-2、IL-6、IL-8、IL-17、NLR、TNFα、CRP、ALT、AST、TBil与无复发组比较,差异均有统计学意义(P值均<0. 05)。Cox模型分析结果显示年龄> 63岁风险比(HR)=2. 391]、肿瘤最大直径> 6 cm(HR=1. 851)、BMI> 27. 17 kg/m^2(HR=1. 546)、IL-17> 10. 8 pg/m1(HR=1. 556)、TNFα> 11. 8 ng/L(HR=1.562)、ALT>42 U/L(HR=1.624)、TBil>15.6μmol/L(HR=1. 534)是HCC患者术后复发的独立危险因素(P值均<0. 05)。采用内部数据进行验证,C-index为0. 724(95%CI:0. 668~0. 824)。结论本研究构建的Nomogram模型能较为准确的预测首次肝切除术的HCC患者复发情况,其临床价值有待更多的研究证实。

Establishment of Nomogram model of postoperative recurrence of primary hepatocellular carcinoma with reference to inflammatory cytokines

Objective To establish the Nomogram model of postoperative recurrence of hepatocellular carcinoma( HCC) by collecting the data on clinical indices and inflammatory cytokines. Methods A total of 314 patients with HCC who were admitted to Wuhan Central Hospital from January 2014 to January 2016 and underwent hepatectomy for the first time were enrolled,and according to follow-up results,these patients were divided into non-recurrence group and recurrence group. General data were collected,and liver function parameters and inflammatory cytokines were measured. The chi-square test was used for comparison of categorical data between two groups,and the Mann-Whitney U test was used for comparison of ranked data between two groups. The receiver operating characteristic( ROC) curve was used to obtain the optimal cut-off values of continuous data. The multivariate Cox proportional hazards model was used to investigate the independent risk factors for recurrence. The Nomogram model was established according to the results of the multivariate Cox proportional hazards model and was validated by internal data,and the consistency index( C-index) was calculated. Results The follow-up time ranged from1 month to 40 months,with a median follow-up time of 13 months. Of all patients,140 had no recurrence,and 174 experienced recurrence. The median recurrence-free survival time was 19 months,and the half-,1-,and 2-year recurrence-free survival rates were68. 2%,57. 3%,and 45. 9%,respectively. There were significant differences between the two groups in age,maximum tumor diameter,body mass index( BMI),interleukin-2,interleukin-6,interleukin-8,interleukin-17( IL-17),neutrophil-lymphocyte ratio,tumor necrosis factor α( TNF α),C-reactive protein,alanine aminotransferase( ALT),aspartate aminotransferase,and total bilirubin( TBil)( all P < 0. 05). The Cox proportional hazards model showed that age > 63 years( hazard ratioHR]= 2. 391,P < 0. 05),maximum tumor diameter > 6 cm( HR = 1. 851,P < 0. 05),BMI > 27. 17 kg/m^2( HR = 1. 546,P < 0. 05),IL-17 > 10. 8 pg/m L( HR = 1. 556,P <0. 05),TNF α> 11. 8 ng/L( HR = 1. 562,P < 0. 05),ALT > 42 U/L( HR = 1. 624,P < 0. 05),and TBil > 15. 6 μmol/L( HR = 1. 534,P < 0. 05) were independent risk factors for postoperative recurrence in patients with HCC. Validation by internal data showed a C-index of0. 724( 95% confidence interval: 0. 668-0. 824). Conclusion The Nomogram model established in this study can accurately predict the recurrence of HCC patients after first-time hepatectomy,but more clinical studies are needed to confirm this result.