甲胎蛋白水平与肝细胞癌预后的相关性分析

Correlation of alpha fetoprotein with the prognosis of hepatocellular carcinoma after hepatectomy in an ethnic Chinese population

目的 探讨肝细胞癌（HCC）患者术前血清甲胎蛋白表达水平与外科治疗后的预后关系.方法 回顾性分析779例外科治疗HCC患者的临床资料,采用Kaplan-Meier法进行生存分析,应用Cox比例风险模型进行多因素回归分析.结果 应用ROC曲线获得中国医学科学院肿瘤医院HCC患者血清甲胎蛋白（AFP）的临界值为18.98 μg/L,此时AFP灵敏度为54.6％,特异度为82.0％.AFP阴性组（AFP ＜20 μg/L）术后1、3、5年生存率分别为94.4％,77.3％和58.9％;AFP阳性组（AFP≥20 μg/L）术后1、3、5年生存率分别为90.6％,64.5％和49.6％ （P =0.005）.Kaplan-Meier单因素分析显示：无临床症状、无腹水、小肝癌（直径≤5 cm）、肿瘤单发、血清AFP低水平表达、血清碱性磷酸酶（ALP）低水平表达、病理分化程度好、病理无脉管瘤栓、无/轻度肝硬化、Child-Pugh A级、无围手术期输血、无腹腔淋巴结转移、无大血管侵犯以及无肿瘤破裂或肝外侵犯是肝癌患者术后较好的预后因素.Cox多因素分析显示：有无临床症状、年龄、肿瘤数目、血清AFP表达水平、血清ALP表达水平、Child-Pugh分级、病理脉管瘤栓、有无腹腔淋巴结转移、有无大血管侵犯、有无肿瘤破裂或肝外侵犯以及术中输血是影响HCC患者长期生存的独立影响因素.分别以阈值1、2、3、5年为界,将总病例分为生存时间大于阈值组及小于阈值组,秩和检验结果表明：血清AFP低表达（18.3 ～23.9μg/L）具有较好的预后,血清AFP＞ 59.3 μg/L患者预后较差,AFP的高表达与患者的不良预后相关,并且血清AFP越高表达患者预后越差（P=0.001）.结论 AFP高表达预示着肿瘤生物学行为较差、肿瘤负荷较大、肝脏背景较差、手术难度和风险及输血比例增加.血清AFP阴性表达患者具有较好的预后,血清AFP表达浓度越高预示患者预后越差.

Objective To explore the correlation between alpha fetoprotein （AFP） and the prognosis of hepatocellular carcinoma after hepatectomy in an ethnic Chinese population.Methods This study retrospectively analyzed the surgical outcomes of hepatocellular carcinoma （HCC） in 779 patients undergoing hepatic resection between June 1999 and March 2010 at our hospital.The postoperative prognostic factors were assessed by univariate Kaplan-Meier analysis and a multivariate Cox proportional hazard model.Results The cut-off value of AFP was 18.98 μg/L by receiver operating characteristic （ROC） curve statistics and the sensitivity and specificity rates were 54.6％ and 82.0％ respectively.The overall survival （OS） rate of AFP negative group （AFP ＜ 20 μg/L） for 1,3 and 5-year was 94.4％,77.3％ and 58.9％ while the OS rate of AFP positive group （AFP≥20 μg/L） for 1,3 and 5-year 90.6％,64.5％ and 49.6％.According to univariate analysis,better prognosis for OS was associated with asymptomatic presentation,no ascites,small tumor,single lesion,serological AFP negativity,serological alkaline phosphatase （ALP） negativity,high-grade histological differentiation,no carcinoma cell embolus,no/mild cirrhosis,Child-Pugh class A,no transfusion,no regional lymph node metastasis,no major vascular invasion,no direct invasion of adjacent organs or with perforation of visceral peritoneum.In multivariate analysis,asymptomatic presentation,young age,single lesion,Alpha-Fetoprotein （AFP） negative expression,serological alkaline phosphatase （ALP） negative expression,Child-Pugh class A,no carcinoma cell embolus,serological no regional lymph node metastasis,no major vascular invasion,no direct invasion of adjacent organs,no perforation of visceral peritoneum and non-transfusion were independent factors for longer OS.Then all patients were classified into different groups by various OS time of 1,2,3,5-year respectively.The statistical results showed that patients with a low expression of serum AFP had better prognosis.Conclusion Lower serum level of AFP indicates better prognosis while higher AFP level is directly correlated with more aggressive biological tumor activities,poor background of liver and poor prognosis.