Annexin A2 is a discriminative serological candidate in early hepatocellular carcinoma

To date, the useful markers of hepatocellular carcinoma (HCC) remains incompletely developed. Here, we show that annexin A2 complement alpha-fetoprotein (AFP), a widely used liver cancer marker, in the serologically surveillance and early detection of HCC. First, differentially expressed proteins in HCC were identified using a subcellular proteomic approach. Annexin A2 was then selected for further verification. It was found to be overexpressed in HCC tissues (60.7%, 136/224). Using a self-estabished sandwich enzyme-linked immunosorbent assay, we found that annexin A2 significantly increased in the sera of HCC (n 175, median, 24.75ng/l) compared with the healthy (n 49, median, 16.69ng/l), benign tumors (n 19, median, 19.92ng/l), hepatitis (n 23, median, 6.48ng/l) and cirrhosis (n 51, median, 7.39ng/l) controls and other malignant tumors (n 87). Importantly, raised concentrations of annexin A2 were observed in 83.2% (79/95) of early stage (median, 24.32ng/l) and 78.4% (58/74) of AFP-negative (median, 24.09ng/l) patients. Annexin A2 alone had a better area under the receiver-operating characteristic curve (AUC 0.79, 95% confidence interval: 0.730.85) in comparison with AFP (AUC 0.73, 95% confidence interval: 0.660.80) in detecting of early stage HCC. Combining both markers notably improved the diagnostic efficiency of early HCC with an achieved sensitivity of 87.4%. Additionally, the expression characteristics of annexin A2 during hepatocarcinogenesis were detected in p21-HBx gene knockin transgenic mice model. The results showed that annexin A2 expression was substantially elevated in HCC-bearing mice, in accordance with the finding in human samples. In conclusion, annexin A2 may be an independent serological candidate for hepatitis B virusrelated HCC, especially in the early stage cases with normal serum AFP.