Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma.
The human aspartyl beta-hydroxylase is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins. The aspartyl beta-hydroxylase gene is upregulated in many human malignancies. The purpose of this study was to investigate the expression of aspartyl beta-hydroxylase in hepatocellular carcinoma. Aspartyl beta-hydroxylase mRNA levels were measured in 161 hepatocellular carcinomas and paired nontumorous liver tissues by conventional and real-time RT-PCR. Immunohistochemical staining of aspartyl beta-hydroxylase was performed using EnVision Plus system. The results showed that aspartyl beta-hydroxylase was overexpressed in 150 of 161 hepatocellular carcinomas (93%), including 45 of 48 unifocal small hepatocellular carcinomas (94%). Aspartyl beta-hydroxylase was highly expressed in hepatocellular carcinoma cells in contrast to its low level of expression in non-neoplastic liver cells. The protein expression level of aspartyl beta-hydroxylase in the hepatocellular carcinoma was parallel with the mRNA expression level (r=0.6594, P<0.0001). A significantly higher tumor aspartyl beta-hydroxylase overexpression level was associated with the presence of intrahepatic metastasis and the progression of histological grades. In conclusion, aspartyl beta-hydroxylase is overexpressed frequently in hepatocellular carcinoma, including early-stage small hepatocellular carcinoma, indicating that overexpression of aspartyl beta-hydroxylase plays a role in the development and progression of hepatocellular carcinoma.
Xian
Zhi-Hong
ZH
Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Zhang
Shu-Hui
SH
Cong
Wen-Ming
WM
Yan
He-Xin
HX
Wang
Kui
K
Wu
Meng-Chao
MC
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D006899:Mixed Function Oxygenases; C058291:aspartic acid 2-oxoglutarate-dependent dioxygenase