title: Repeated-measures implication of hepatocellular carcinoma biomarkers in living donor liver transplantation.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) and its recurrence are major problems in living donor liver transplantation (LDLT). Several biomarkers have been used to investigate this event. We conducted a prospective controlled study to determine the activities of the basic fibroblast growth factor (FGF-2), survivin, Ki67, endostatin, and vascular endothelial growth factor (VEGF) in different conditions before, early after, and late after LDLT with and without HCC recurrence.
  
  
  METHODS
  Fifty patients with virus-related HCC who underwent LDLT were enrolled in this 2-year cross-sectional study. During the study period, recurrent HCC was identified in 9 patients (study group, n = 9) and 41 patients (control group, n = 41) had no recurrence after LDLT. The mean time to HCC recurrence was 587.11 ± 398.64 days (range, 90-1352 days). Microvascular invasion (MVI) was found in 66.7% (6/9) of the recipients, as determined on pathological examination. The serum biomarkers were investigated by using enzyme-linked immunosorbent assay at the different LDLT stages.
  
  
  RESULTS
  The serum levels of the biomarkers significantly correlated with LDLT and HCC recurrence in the repeated-measures analysis (F = 31.676, P = 0.000). Significant differences were observed in the effects of all biomarkers (F = 85.313, P = 0.000) and the time to HCC recurrence after LDLT (F = 3.178, P = 0.046). The biomarkers, ordered by the observed power of the test for HCC recurrence after LDLT, were FGF-2 (1.000) > survivin (0.999) > Ki67 (0.949) > endostatin (0.411) > VEGF (0.305).
  
  
  CONCLUSIONS
  Different biomarker activities may be implicated in the pathogenesis of HCC recurrence after LDLT. Oncogenes may not exist in the new graft but may still be present in the peripheral blood. The timing of HCC recurrence and impact of MVI in the explanted liver requires confirmation in larger studies with a longer follow-up.
authors.affiliation: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: King-Wah
authors.initials: KW
authors.lastname: Chiu
authors.affiliation: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Kuang-Den
authors.initials: KD
authors.lastname: Chen
authors.affiliation: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Hsu
authors.affiliation: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.affiliation: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Ching-Yin
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Cheng
authors.affiliation: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.affiliation: Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000601:surgery*; D043169:Endostatins / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000097:blood; D019394:Ki-67 Antigen / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood* / Q000601:surgery*; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000077022:Survivin; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: C107489:BIRC5 protein, human; D015415:Biomarkers; D043169:Endostatins; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2