Expression of MAGE, GAGE and BAGE genes in human liver diseases: utility as molecular markers for hepatocellular carcinoma.
OBJECTIVE
The MAGE, GAGE and BAGE genes encode tumor antigens recognized by autologous cytotoxic T lymphocytes. The aim of this study was to evaluate the possibility of using these genes as molecular markers and as the targets of specific immunotherapy for human hepatocellular carcinoma (HCC).


METHODS
The expressions of MAGE-1, MAGE-3, GAGE1-6, GAGE1-2 and BAGE mRNA in 33 surgically resected HCC samples and 26 of their corresponding non-cancerous samples (11 liver cirrhosis and 15 chronic hepatitis) were studied by a reverse-transcription polymerase chain reaction, and were compared with clinicopathological parameters. The expression of MAGE-1 was also examined in 16 biopsied HCC samples.


RESULTS
MAGE-1, MAGE-3, GAGE1-6, GAGE1-2 and BAGE mRNA were expressed in 67%, 39%, 36%, 30%, and 21% of the HCC, respectively. At least one transcript was detected in 88% of the HCC, while no expression was observed in the non-cancerous livers. There was no significant correlation between the expression of any of the tumor antigens examined and the differentiation stage or size of the HCC. Especially, MAGE-1 was highly expressed in small HCC with a diameter of less than 2 cm and in well-differentiated HCC (81% and 70%, respectively), and was also expressed even in alpha-fetoprotein-negative and PIVKA-II-negative HCC (58% and 76%, respectively). The MAGE-1 expression was detected in 69% of biopsied HCC samples and the expression was high in both small and well-differentiated HCC.


CONCLUSIONS
These tumor-specific antigens can be useful as molecular markers and as the possible target molecules for the specific immunotherapy of human HCC.
Kobayashi
Y
Y
The First Department of Internal Medicine, Okayama University Medical School, Okayama-City, Japan.
Higashi
T
T
Nouso
K
K
Nakatsukasa
H
H
Ishizaki
M
M
Kaneyoshi
T
T
Toshikuni
N
N
Kariyama
K
K
Nakayama
E
E
Tsuji
T
T
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics
D000951:Antigens, Neoplasm; C092706:BAGE protein, human; D014408:Biomarkers, Tumor; C095365:GAGE1 protein, human; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins