Increased expression of a disintegrin and metalloprotease-9 in hepatocellular carcinoma: implications for tumor progression and prognosis.
OBJECTIVE
A disintegrin and metalloprotease-9 has been involved in the carcinogenesis of various solid tumors. However, its role in hepatocellular carcinoma remains unknown. The aim of this study was to investigate the clinicopathological and prognostic relevance of a disintegrin and metalloprotease-9 by immunohistochemistry.


METHODS
The expression profile of a disintegrin and metalloprotease-9 in association with the clinicopathological factors was determined by immunohistochemical analysis in hepatocellular carcinoma patients, and its potential prognostic value was investigated by comparing the survival rate between a disintegrin and metalloprotease-9-positive and a disintegrin and metalloprotease-9-negative patients.


RESULTS
Hepatocellular carcinoma tissues with positive a disintegrin and metalloprotease-9 expression were larger and less differentiated than those with negative expression (P = 0.02 and 0.008, respectively). Portal venous invasion, hepatic venous invasion, bile duct invasion and intrahepatic metastasis were detected significantly more frequently in a disintegrin and metalloprotease-9-positive group (P = 0.009, 0.01, 0.03 and 0.02, respectively). In addition, high alpha-fetoprotein levels were significantly associated with the expression of a disintegrin and metalloprotease-9 in hepatocellular carcinoma (P = 0.01). Moreover, a disintegrin and metalloprotease-9-positive group had significantly poorer outcomes than a disintegrin and metalloprotease-9-negative group (P = 0.01) and was an independent prognostic factor for overall survival.


CONCLUSIONS
A disintegrin and metalloprotease-9 is over-expressed in hepatocellular carcinoma tissues, consistent with findings in other tumor entities, and is an independent prognostic marker of overall survival following hepatectomy. Further studies are needed to investigate the precise function of a disintegrin and metalloprotease-9 in the progression of hepatocellular carcinoma.
Tao
KaiShan
K
Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China. tao.prof@gmail.com
Qian
NianSong
N
Tang
Yu
Y
Ti
Zhenyu
Z
Song
WenJie
W
Cao
DaYong
D
Dou
KeFeng
K
D051722:ADAM Proteins / Q000378:metabolism*; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D051722:ADAM Proteins; C098339:ADAM9 protein, human