Evaluation of MAGE-D4 expression in hepatocellular carcinoma in Japanese patients.
OBJECTIVE
Though Melanoma-associated antigen (MAGE) family genes have received lots of attention as cancer-related genes and targets for immunotherapy, MAGE-D4 expression in hepatocellular carcinoma (HCC) has not yet been evaluated.


METHODS
MAGE-D4 mRNA expression was assayed in nine HCC cell lines and 94 HCC surgical specimens obtained from Japanese patients by quantitative real-time reverse transcription polymerase chain reaction, and the correlations between MAGE-D4 mRNA expression and clinicopathological factors were evaluated. The expression and distribution of MAGE-D4b protein were evaluated immunohistochemically.


RESULTS
MAGE-D4 mRNA was overexpressed in five of nine HCC cell lines and 34 of 94 primary HCCs (36.2%). Median overall survival (14.8 vs. 118 months, P < 0.001) and relapse-free survival (2.7 vs. 18.3 months, P < 0.001) were significantly shorter in patients with high than with low-moderate MAGE-D4 expression. Multivariate analysis for overall survival showed that MAGE-D4 overexpression was independently prognostic for survival (hazard ratio 2.88, P = 0.009) and significantly associated with high alpha-fetoprotein concentration (P < 0.001), poor tumor differentiation (P = 0.003) and vascular invasion (P = 0.021). MAGE-D4b protein expression patterns were consistent with those of MAGE-D4 mRNA.


CONCLUSIONS
Overexpression of MAGE-D4 may be a predictive marker of early recurrence and mortality in patients with HCC.
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hideki
H
Takami
Mitsuro
M
Kanda
Hisaharu
H
Oya
Soki
S
Hibino
Hiroyuki
H
Sugimoto
Masaya
M
Suenaga
Suguru
S
Yamada
Yoko
Y
Nishikawa
Mikako
M
Asai
Tsutomu
T
Fujii
Shuji
S
Nomoto
Yasuhiro
Y
Kodera
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics; D044466:Asian People; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008099:Liver / Q000737:chemistry; D008113:Liver Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000737:chemistry* / Q000175:diagnosis / Q000401:mortality; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000032:analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C120897:MAGED1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000509:alpha-Fetoproteins
MAGE-D4; hepatocellular carcinoma; progression; recurrence