title: Elevation of serum γ-glutamyltransferase as a predictor of aggressive tumor behaviors and unfavorable prognosis in patients with intrahepatic cholangiocarcinoma: analysis of a large monocenter study.
abstract: OBJECTIVE
  γ-Glutamyltransferase (GGT) has been used as a diagnostic biomarker for hepatobiliary disease. However, little is known about its role in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to validate the clinical significance of GGT in predicting the prognosis of ICC patients.
  
  
  METHODS
  A total of 411 patients with pathologically confirmed ICC were retrospectively analyzed. Of them, 307 patients underwent hepatectomy, 64 patients with unresectable tumors were treated with chemotherapy (n=42) or transcatheter arterial chemoembolization (n=22), and 40 patients with end-stage disease received supportive treatment. The association between GGT and the clinicopathological features and prognosis was assessed.
  
  
  RESULTS
  Serum GGT levels were significantly associated with hepatitis B infection (P=0.02), the Child-Pugh grade (P=0.02), vascular invasion (P<0.001), lymph node involvement (P=0.04), and incomplete tumor encapsulation (P=0.009). Survival analysis showed that GGT was an independent predictor of a poor prognosis (hazard ratio=2.36, 95% confidence interval: 1.67-3.34, P=0.001). This prognostic value of GGT was further validated in the mass-forming, normal bilirubin, and Child-Pugh A subgroups. Subsequent recurrence analysis showed that a recurrence-free survival in patients with high GGT levels was significantly shorter than that in those with low GGT levels (6 vs. 12 months, P<0.001). The serum GGT level was an independent predictor of tumor recurrence in ICC patients (hazard ratio=1.59, 95% confidence interval: 1.07-2.37, P=0.02).
  
  
  CONCLUSIONS
  Elevation of serum GGT levels is an indicator of aggressive tumor behaviors and a predictor of poor clinical outcomes. It may prove to be a useful biomarker for identifying ICC patients at high risk of early recurrence and unfavorable prognosis.
authors.affiliation: Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute & Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yin
authors.forename: Su-Su
authors.initials: SS
authors.lastname: Zheng
authors.forename: Bo-Heng
authors.initials: BH
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Chen
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Ren
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000097:blood*; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000473:pathology / Q000556:secondary / Q000628:therapy; D004796:Clinical Enzyme Tests / Q000379:methods; D018450:Disease Progression; D005260:Female; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000556:secondary / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human