Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 7, 2012; 18(41): 5897-5904
Published online Nov 7, 2012. doi: 10.3748/wjg.v18.i41.5897
Expression characteristics and diagnostic value of annexin A2 in hepatocellular carcinoma
Hai-Jian Zhang, Deng-Fu Yao, Min Yao, Hua Huang, Wei Wu, Mei-Juan Yan, Xiao-Di Yan, Jie Chen
Hai-Jian Zhang, Deng-Fu Yao, Wei Wu, Xiao-Di Yan, Jie Chen, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Min Yao, Mei-Juan Yan, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
Hua Huang, Departments of Pathology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Author contributions: Zhang HJ and Yao M contributed equally to this work, designed the research, analyzed the data, and wrote the first draft; Yan XD and Chen J collected liver specimens; Yan MJ performed quantitative real time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay analysis; Wu W and Huang H performed immunohistochemistry and evaluation; Yao DF is the guarantor and contributed to the design and interpretation of the study.
Supported by Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD); the Project of Jiangsu Clinical Medicine (BL2012053); the Programs of Nantong Society Undertaking and Technological Innovation, No. HS2012034 and HS2011012; the International S and T Cooperation Program of China
Correspondence to: Deng-Fu Yao, MD, PhD, Professor, Research Centre of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong 226001, Jiangsu Province, China. yaodf@ahnmc.com
Telephone: +86-513-85052297 Fax: +86-513-85052254
Received: May 26, 2012
Revised: August 23, 2012
Accepted: August 25, 2012
Published online: November 7, 2012
Abstract

AIM: To investigate the characteristics and diagnostic value of annexin A2 (ANXA2) expression in cancerous tissues and sera of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

METHODS: Levels of liver ANXA2 gene transcription or protein expression were analyzed in HCC-, their self-controlled precancerous-, and distant cancerous- tissues from 30 HCC. Serum levels of ANXA2 expression in 115 patients with HCC, 25 with metastatic liver cancer, 35 with chronic hepatitis, 28 with acute hepatitis, 38 with cirrhosis, and 30 healthy controls were determined. Clinicopathological characteristics of circulating ANXA2 expression were analyzed, and its diagnostic efficiency and clinical values in HCC were evaluated.

RESULTS: ANXA2 expression was localized in both cell membrane and cytoplasm in HCC tissue, mainly in the cytoplasm of matched adjacent cancerous tissue, and there was almost no positive staining in matched distant cancerous tissue. Abnormal expression of liver ANXA2 was present in HCC tissues compared with self-controlled adjacent- and distant-cancerous tissues at protein or mRNA level. Circulating ANXA2 in HCC patients was significantly higher than that of other liver diseases (P < 0.01) except metastatic liver cancer. If the diagnostic cutoff value of ANXA2 level was more than 18 ng/mL, the incidence of serum ANXA2 was 86.96% in the HCC group, 80% in the metastatic liver cancer group, 31.58% in the liver cirrhosis group, none in the chronic hepatitis or acute hepatitis or normal control group, respectively. Serum ANXA2 expression in HCC patients was correlated with HBV infection (27.38 ± 5.67 ng/mL vs 18.58 ± 7.83 ng/mL, P < 0.01), extrahepatic metastasis (26.11 ± 5.43 ng/mL vs 22.79 ± 5.64 ng/mL, P < 0.01), and portal vein thrombus (26.03 ± 5.99 ng/mL vs 23.06 ± 5.03 ng/mL, P < 0.01), and was significantly higher (P < 0.01) in the moderately- (26.19 ± 5.34 ng/mL) or the poorly- differentiated group (27.05 ± 5.13 ng/mL) than in the well differentiated group (20.43 ± 4.97 ng/mL), and in the tumor node metastasis stages III-IV (P < 0.01) than in stages I-II. ANXA2 was not correlated with patient sex, age, size or α-fetoprotein (AFP) level. Area under the receiver operating characteristic curve for the whole range of sensitivities and specificities was 0.796 for ANXA2 and 0.782 for AFP. Combining detection of serum ANXA2 and AFP substantially improved the diagnostic efficiency (96.52%) and the negative predictive value (96.61%) for HCC.

CONCLUSION: The characteristics and distribution of ANXA2 expression has good diagnostic potential for HCC diagnosis.

Keywords: Hepatocellular carcinoma; Annexin A2; Liver; Upregulation; Clinicopathological characteristics; Diagnosis; Expression; Biomarker