title: Annexin A2 is a discriminative serological candidate in early hepatocellular carcinoma.
abstract: 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-established sandwich enzyme-linked immunosorbent assay, we found that annexin A2 significantly increased in the sera of HCC (n = 175, median, 24.75 ng/µl) compared with the healthy (n = 49, median, 16.69 ng/µl), benign tumors (n = 19, median, 19.92 ng/µl), hepatitis (n = 23, median, 6.48 ng/µl) and cirrhosis (n = 51, median, 7.39 ng/µl) controls and other malignant tumors (n = 87). Importantly, raised concentrations of annexin A2 were observed in 83.2% (79/95) of early stage (median, 24.32 ng/µl) and 78.4% (58/74) of AFP-negative (median, 24.09 ng/µl) patients. Annexin A2 alone had a better area under the receiver-operating characteristic curve (AUC = 0.79, 95% confidence interval: 0.73-0.85) in comparison with AFP (AUC = 0.73, 95% confidence interval: 0.66-0.80) 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 virus-related HCC, especially in the early stage cases with normal serum AFP.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Sun
authors.forename: Guangzhou
authors.initials: G
authors.lastname: Gao
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Cai
authors.forename: Youliang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Qu
authors.forename: Lidong
authors.initials: L
authors.lastname: He
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Yangjun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kaixuan
authors.initials: K
authors.lastname: Lin
authors.forename: Shouzhi
authors.initials: S
authors.lastname: Ma
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Qian
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017306:Annexin A2 / Q000097:blood* / Q000378:metabolism; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D012372:ROC Curve; D046888:Tissue Array Analysis; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins