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

Abstract

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.