The loss of phenol sulfotransferase 1 in hepatocellular carcinogenesis.
Biomarkers for the detection of early hepatocellular carcinoma (HCC) are urgently needed. To identify biomarkers of HCC, we performed a comparative proteomics analysis, based on 2-DE of HCC tissues and surrounding non-tumor tissues. Six xenobiotic enzymes were significantly down-regulated in the HCC tissue. Among these, phenol sulfotransferase (SULT1A1) was confirmed by Western blot analysis in 105 HCC patients. SULT1A1 showed a significant decrease in 98.1% of the HCC tissues, with 88.6% sensitivity and 66.7% specificity for the detection of HCC. Immunohistochemistry for SULT1A1 was performed and compared with glypican-3, which is a well-known marker of HCC. The results showed down-regulation of SULT1A1 and up-regulation of glypican-3 in 52.6 and 71.9% of the HCCs, and the use of both markers improved the sensitivity up to 78.9%. Moreover, SULT1A1 was useful in differentiating early HCC from benign dysplastic nodules. Clinically, the down-regulation of SULT1A1 was closely associated with an advanced International Union Against Cancer stage and high levels of serum alpha-fetoprotein. In conclusion, the results of this study demonstrate that the loss of SULT1A1 appears to be a characteristic molecular signature of HCC. SULT1A1 might be a useful biomarker for the detection of early HCC and help predict the clinical outcome of patients with HCC.
Yeo
Marie
M
Genome Research Center for Gastroenterology, Ajou University School of Medicine, Suwon 442-749, Korea.
Na
Young Mi
YM
Kim
Dong Kyu
DK
Kim
Young Bae
YB
Wang
Hee Jeong
HJ
Lee
Jung A
JA
Cheong
Jae Youn
JY
Lee
Kwang Jae
KJ
Paik
Young-Ki
YK
Cho
Sung Won
SW
D000595:Amino Acid Sequence; D015239:Arylsulfotransferase / Q000737:chemistry / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D053673:Glypicans / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000509:alpha-Fetoproteins / Q000378:metabolism
D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans; D000509:alpha-Fetoproteins; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human