title: Expression characteristics and diagnostic value of annexin A2 in hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The characteristics and distribution of ANXA2 expression has good diagnostic potential for HCC diagnosis.
authors.affiliation: Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Deng-Fu
authors.initials: DF
authors.lastname: Yao
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Yan
authors.forename: Xiao-Di
authors.initials: XD
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000097:blood* / Q000235:genetics; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D015854:Up-Regulation
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D014408:Biomarkers, Tumor
keywords: Annexin A2; Biomarker; Clinicopathological characteristics; Diagnosis; Expression; Hepatocellular carcinoma; Liver; Upregulation