Wnt3a作为新标志物对肝癌诊断和预后的临床价值

Clinical values of Wnt3a as a novel biomarker in diagnosis and prognosis of hepatocellular carcinoma

目的分析检测肝细胞性肝癌（HCC）患者癌组织和血Wnt3a的表达，探讨其对HCC诊断及预后的临床价值。方法以组织芯片、免疫组织化学法及特异性抗体测定法，检测80例肝癌及癌周组织中Wnt3a表达，结合随访数据评估其预后价值。用酶联免疫吸附法检测肝癌、肝硬化、慢炎肝炎患者血清Wnt3a水平，并与甲胎蛋白（AFP）比较评估Wnt3a诊断价值。结果定位于胞质和细胞膜的Wnt3a在肝癌组织阳性率为96．3％，显著高于癌周组织的46．3％（χ^2=48．818，P〈0．001）；其表达与肝癌的分化程度、是否伴肝硬化、HBV感染和TNM分期均显著相关（P〈0．05），高表达者5年生存率显著降低（P〈0．001），为HCC预后的独立预测因素。癌组织合成的Wnt3a分泌人血，其水平大约是肝硬化组4．0倍，慢性肝炎组9．2倍，健康对照组26．7倍，与肝硬化、乙型肝炎病毒（HBV）感染、分化程度、TNM分期和肝外转移等显著相关（P〈0．05）；如以800ng／L为正常上限，诊断肝癌的敏感度、特异度、准确度、阳性预测值和阴性预测值分别为92．5％，94．3％，93．2％，96．1％和89．3％，与AFP联检提高阳性率至96．3％；ROC曲线下面积为0．99显著高于AFP的0．71（P〈0．001）。结论Wnt通路关键信号分子Wnt3a表达与肝癌进展密切相关，为新HCC特异诊断和预后的标志物。

Objective To explore Wnt3a expression in HCC tissues and serum, and to discuss its clinical diagnostic and prognostic value. Methods The Wnt3a expressions were detected in a total of 186 patients （HCC, liver cirrhosis and chronic Hepatitis ） and 40 controls by Elisa, comparing with AFP to evaluate its clinical diagnosis value. Wnt3a expressions in 80 HCC and surrounding tissues were analyzed by IHC,to explore its prognostic value. Results Wnt3a with brown staining was mainly distributed in cytosol and of hepatocyte membrane. The higher expression （ 3 - 6 scores ） was 71.3% in HCC, 13.8% in surrounding tissues, associated with poorly-differentiated grade, liver cirrhosis, HBV infection, higher TNM stage （P 〈 0. 05 ） and 5-year survival rate （P 〈 0. 001 ）, identified as independent predictive factors for poor HCC outcome and closely related with lower five-year survival rate. Serum average Wnt3a levels were significantly higher （ P 〈 0. 001 ） in the HCC group than those in any other groups of benign liver diseases, with about 4. 0, 9. 2 and 26.7 times higher than that in the liver cirrhosis, chronic hepatitis and normal control group. Wnt3a expression in HCC were closely related to AFP concentration, liver cirrhosis HBV infection, poor differentiation, TNM stagingand extra- hepatic metastasis （ P 〈 0. 05 ）. The sensitivity, specificity, accuracy, positive predictive value and negative predictive values were 92. 5,94. 3, 93.2, 96. 1 and 89. 3% at 800 ng/L as cutoff value for Wnt3a. Combining Wnt3a and AFP test, the total sensitivity could rise to 96. 3%. The area under ROC curve in Wnt3a （0. 994） was higher than in AFP （0. 710）. Conclusions Wnt3a as a critical signal molecule in the Wnt pathway is a new specific marker for HCC diagnosis and prognosis.