title: Tie2-Expressing Monocytes Are Associated with Identification and Prognoses of Hepatitis B Virus Related Hepatocellular Carcinoma after Resection.
abstract: BACKGROUND
  Tie2-expressing monocytes (TEMs) are found in various tumors, involved in forming tumor blood vessels and expressing several important proangiogenic factors. The goals of this study were to evaluate the value of TEMs in diagnosing and predicting the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
  
  
  METHODS
  Flow cytometry was performed to identify and count TEMs in peripheral blood monocytes from HCC patients (n = 84) receiving hepatectomy, HBV cirrhotic patients (n = 21), benign tumors patients (n = 15) and healthy volunteers (n = 23). Angiopoietin-2 (Ang-2) levels in the plasma were determined by enzyme linked immunosorbent assay. The distribution of TEMs in tumor tissue was observed by immunofluorescence staining. Then we determined the vascular area as a percentage of tumor area (vascular area/tumor area) by immunohistochemical staining. Finally the prognostic significance of TEMs and other clinicopathologic factors was evaluated.
  
  
  RESULTS
  Percentage of TEMs in peripheral blood monocytes significantly increased in HCC patients compared with HBV cirrhotic patients and healthy donors (both P< 0.001). However there was no significance in benign liver tumor (P = 0.482). In addition, the percentage of circulating TEMs was positively correlated with plasma Ang-2 concentration (P<0.001, r2 = 0.294) and vascular area/tumor area (P<0.001, r2 = 0.126). Furthermore the percentage of intratumoral TEMs was significantly higher than that of paratumoral TEMs (P<0.001). Increased circulating TEMs was associated with poor overall survival (P = 0.043) and a shorter time to recurrence (P = 0.041). Multivariate Cox analysis also revealed that the percentage of TEMs in peripheral blood was an independent factor for HCC patients' prognosis.
  
  
  CONCLUSIONS
  TEMs may promote angiogenesis in HCC regarding the angiopoietin/Tie2 signal pathway. Percentage of TEMs in peripheral blood monocytes may be applied as a biomarker for identifying HBV-related HCC and predicting the prognosis of these patients after resection.
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: He
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Chao-Qun
authors.initials: CQ
authors.lastname: Wang
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Immunology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
authors.forename: Qi-Man
authors.initials: QM
authors.lastname: Sun
authors.affiliation: Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.|Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006515:Hepatitis B virus / Q000472:pathogenicity*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D042787:Receptor, TIE-2 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D042787:Receptor, TIE-2