Effects of Toll like receptor 4 and hepatocyte growth factor expression levels on prognosis of patients with hepatocellular carcinoma after radical resection
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摘要:目的 探讨术前血清Toll样受体4（TLR4）、肝细胞生长因子（HGF）表达水平对肝细胞癌患者切除术后预后的影响。方法 选取78例肝细胞癌患者作为研究对象，均接受肝细胞癌切除术治疗并随访1年，依据随访1年时预后情况（带瘤生存或无瘤生存）将患者分为预后不良组与预后良好组。记录并比较2组患者的基线资料，术前检测患者的血清TLR4、HGF水平，并分析术前血清TLR4、HGF水平对肝细胞癌患者肝细胞癌切除术后预后的影响。结果 随访1年时，预后不良患者16例，占20.51%（16/78）；预后不良组患者血清甲胎蛋白（AFP）、α-L-岩藻糖苷酶（AFU）、TLR4、HGF水平均高于预后良好组，差异有统计学意义（P＜0.05）；2组基线资料及其他实验室指标水平比较，差异无统计学意义（P＞0.05）。多因素Logistic回归分析结果显示，术前血清AFP、AFU、TLR4和HGF高水平是肝细胞癌患者术后预后不良的危险因素（OR＞1，P＜0.05）；受试者工作特征曲线显示，术前血清TLR4、HGF水平单独及联合检测预测肝细胞癌患者术后预后的曲线下面积均＞0.70，具有一定的预测价值；TLR4、HGF的cut-off值分别取13.629、0.608 ng/mL时，可获得最佳预测价值。结论 肝细胞癌患者肝细胞癌切除术后预后可能受术前血清TLR4、HGF水平的影响。Abstract:Objective To explore effects of serum Toll like receptor 4 (TLR4) and hepatocyte growth factor (HGF) expression levels on prognosis of patients with hepatocellular carcinoma after radical resection.Methods A total of 78 patients with hepatocellular carcinoma were selected as research subjects, and all received hepatocellular carcinoma resection and were followed up for 1 year. The patients were divided into poor prognosis group and good prognosis group according to the prognosis of patients at 1 year of follow-up (according to the conditions of patients surviving with or without tumors). The baseline data questionnaire of patients was recorded and compared. Serum TLR4 and HGF levels of patients were detected before surgery, and the effects of serum TLR4 and HGF levels on the prognosis of patients with hepatocellular carcinoma after hepatocellular carcinoma resection were analyzed.Results At one year of follow-up after liver radical resection, 16 patients had poor prognosis, accounting for 20.51% (16/78); the serum levels of Serum alpha-fetoprotein (AFP), α-L-fucosidase (AFU), TLR4 and HGF of patients in the poor prognosis group were higher than those in the good prognosis group (P < 0.05); there were no significant differences in baseline data and other laboratory indicators between the two groups (P > 0.05); Logistic regression analysis results showed that high preoperative serum levels of AFP, AFU, TLR4 and HGF were risk factors for poor prognosis of patients with hepatocellular carcinoma after liver radical resection (OR > 1, P < 0.05); the receiver operating characteristic curve showed that the AUC of preoperative serum levels of TLR4 and HGF alone and their combination in predicting the prognosis of patients with hepatocellular carcinoma after liver radical resection were all over 0.70, which had certain predictive value; when the cut-off values of each index were 13.629 ng/mL and 0.608 ng/mL respectively, the best predictive value could be obtained.Conclusion The prognosis of patients with hepatocellular carcinoma after liver radical resection may be affected by the preoperative serum levels of TLR4 and HGF.
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表 1 2组患者基线资料和实验室指标结果比较(x±s)[n(%)][M(P25, P75)]
指标 预后不良组(n=16) 预后良好组(n=62) χ2/t/Z/U P 年龄/岁 52.00(49.00, 55.00) 51.00(49.00, 53.50) 0.702 0.483 性别 男 15(93.75) 51(82.26) 0.558 0.455 女 1(6.25) 11(17.74) 高血压病 有 4(25.00) 10(16.13) 0.211 0.646 无 12(75.00) 52(83.87) 糖尿病 有 3(18.75) 4(6.45) 1.090 0.297 无 13(81.25) 58(93.55) 大量饮酒史 有 11(68.75) 36(58.06) 0.606 0.436 无 5(31.25) 26(41.94) 病灶最大径/cm 3.00±0.55 3.24±1.10 0.793 0.428 TNM分期 Ⅱ期 5(31.25) 38(61.29) 1.876 0.061 Ⅲ期 11(68.75) 24(38.71) 手术时间/h 10.00±2.30 9.38±2.34 0.826 0.409 术中出血量/mL 1 256.00(1 163.50, 1 297.00) 1 310.00(1 232.00, 1 393.00) 1.395 0.163 ALT/(U/L) 77.17±4.65 76.81±4.65 0.260 0.795 AST/(U/L) 58.74±3.55 58.36±3.66 0.368 0.713 AFP/(ng/mL) 513.60±48.16 438.21±58.83 3.924 ＜0.001 AFU/(μmol/L) 526.65±52.79 487.73±43.67 2.371 0.018 TLR4/(ng/mL) 15.72±3.48 11.66±2.75 3.693 ＜0.001 HGF/(ng/mL) 0.68±0.19 0.46±0.16 3.766 ＜0.001 ALT: 谷丙转氨酶; AST: 谷草转氨酶; AFP: 甲胎蛋白; AFU: α-L-岩藻糖苷酶; TLR4: Toll样受体4; HGF: 肝细胞生长因子。 
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表 2 自变量类型与赋值情况
自变量 变量类型 赋值 TNM分期 分类变量 1=Ⅲ期，0=Ⅱ期 AFP 连续变量 - AFU 连续变量 - TLR4 连续变量 - HGF 连续变量 - AFP: 甲胎蛋白; AFU: α-L-岩藻糖苷酶;
TLR4: Toll样受体4; HGF: 肝细胞生长因子。
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表 3 前血清TLR4、HGF水平对肝细胞癌患者术后预后影响的回归分析
相关因素 β 标准误 Wald P OR 95%置信区间 TNM分期 1.510 1.191 1.607 0.205 4.526 0.438~46.724 AFP 0.026 0.012 4.690 0.030 1.026 1.002~1.050 AFU 0.022 0.011 4.007 0.045 1.022 1.000~1.043 TLR4 0.472 0.230 4.213 0.040 1.603 1.022~2.515 HGF 8.054 3.834 4.412 0.036 3 146.129 1.713~5 776 642.632 常量 -36.585 9.840 13.823 ＜0.001 - - AFP: 甲胎蛋白; AFU: α-L-岩藻糖苷酶; TLR4: Toll样受体4; HGF: 肝细胞生长因子。
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表 4 术前血清TLR4、HGF单独及联合对肝细胞癌患者术后预后的预测价值
项目 AUC cut-off值 AUC的95%置信区间 P 特异度 敏感度 约登指数 TLR4 0.808 13.629 ng/mL 0.672~0.945 ＜0.001 0.762 0.733 0.495 HGF 0.814 0.608 ng/mL 0.676~0.953 ＜0.001 0.857 0.800 0.657 联合 0.822 - 0.691~0.953 ＜0.001 0.794 0.800 0.594 TLR4: Toll样受体4; HGF: 肝细胞生长因子; AUC: 曲线下面积。
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