title: Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma.
abstract: OBJECTIVE
  To investigate the biological role of alpha fetoprotein (AFP) and its clinical significance in carcinogenesis of hepatocellular carcinoma (HCC).
  
  
  METHODS
  Clinical analysis of HCC patients and immunohistochemical examination were conducted to evaluate the relationship between serum AFP level and patient mortality. Confocal microscopy, Western blotting, dimethylthiahzolyl-2,5-diphenyl-tetrazolium bromide, Cell Counting Kit-8 assays and flow cytometry were performed to explore the possible mechanism.
  
  
  RESULTS
  Among the 160 HCC patients enrolled in this study, 130 patients survived 2 years (81.25%), with a survival rate of 86.8% in AFP < 2 0 μg/L group, 88.9% in AFP 20-250 μg/L group, and 69.6% in AFP > 250 μg/L group, demonstrating a higher mortality rate in HCC patients with higher AFP levels. Surgical treatment was beneficial only in patients with low AFP levels. The mortality rate of HCC patients with high AFP levels who were treated surgically was apparently higher than those treated with conservative management. The results of immunohistochemistry showed that AFP and AFP receptor were merely expressed in tissues of HCC patients with positive serum AFP. Consistently, in vitro analysis showed that AFP and AFPS were expressed in HepG2 but not in HLE cells. AFP showed a capability to promote cell growth, and this was more apparent in HepG2 cells, in which the proliferation was increased by 3.5 folds. Cell cycle analysis showed that the percentage of HepG2 cells in S phase after exposure to AFP was modestly increased.
  
  
  CONCLUSIONS
  HCC patients with higher AFP levels show a higher mortality rate, which appears to be attributable to the growth promoting properties of AFP.
authors.affiliation: Department of Hepatology and Gastroenterology, Beijing You'an Hospital, Beijing 100069, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Michael A
authors.initials: MA
authors.lastname: McNutt
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Hui-Guo
authors.initials: HG
authors.lastname: Ding
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D018000:Receptors, Peptide / Q000378:metabolism; D012189:Retrospective Studies; D015996:Survival Rate; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018000:Receptors, Peptide; D000509:alpha-Fetoproteins; C042144:alpha-fetoprotein receptor, human