Expression of the MAGE-1 gene in human hepatocellular carcinomas.
OBJECTIVE
To further investigate the expression of MAGE-1 gene in hepatocellular carcinoma (HCC).


METHODS
The tumors and adjacent liver tissue from 45 HCC patients and liver tissue from 28 non-HCC patients (16 with liver cirrhosis and 12 with normal liver) were characterized by RT-PCR. A 421 bp PCR product from a cDNA fragment spanning exons 1, 2 and 3 was sequenced. The HLA type was assayed by standard ELISA in 43 HCC patients.


RESULTS
Thirty-two of 45 tumor tissues from HCC patients expressed MAGE-1 mRNA (71.1%). In contrast, MAGE-1 mRNA was not detected in adjacent tissues. Three were found to have point mutations at 3 identical sites resulting in the substitution of two amino acid residues. The most frequent HLA types in 43 HCC patients were: HLA-A2, 53.5%; A11, 25.6%; A24, 20.9%; A33, 20.9%; HLA-B13, 28.3% and B35, 23.2%. Expression of HLA-A33 (20.9%) was higher in HCC patients than that predicted in the normal Chinese population (8.8%). There was no discemable correlation between MAGE-1 expression and alpha-FP level, tumor size and hepatitis B or C virus infection. The identification of peptides which are restricted by haploptypes other than A1 should increase the opportunity for peptide based immunotherapy.


CONCLUSIONS
This study shows that MAGE-1 mRNA is highly expressed in HCC tumor tissue in Chinese patients. Previously unreported point mutations in the MAGE-1 gene are described and may also provide additional opportunities for immunotherapy.
Chen
H
H
Hepatology Institute, People's Hospital, Peking University, Beijing 100044, China.
Cai
S
S
Wang
Y
Y
Zhao
H
H
Peng
J
J
Pang
X
X
Zhu
J
J
Cong
X
X
Rui
J
J
Leng
X
X
Du
R
R
Wang
Y
Y
Vaughan
H
H
Cebon
J
J
Burgess
A W
AW
Chen
W
W
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D006680:HLA Antigens; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger