Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Surg Oncol. 2013 Dec;108(8):557-62. doi: 10.1002/jso.23440. Epub 2013 Sep 20.
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.
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.
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.
Overexpression of MAGE-D4 may be a predictive marker of early recurrence and mortality in patients with HCC.
尽管黑色素瘤相关抗原（MAGE）家族基因作为癌症相关基因和免疫治疗靶点受到了广泛关注，但 MAGE-D4 在肝细胞癌（HCC）中的表达尚未得到评估。
通过实时定量逆转录聚合酶链反应（qRT-PCR）检测 9 种 HCC 细胞系和 94 例日本 HCC 手术标本中 MAGE-D4mRNA 的表达，并评估 MAGE-D4mRNA 表达与临床病理因素的相关性。采用免疫组织化学法评估 MAGE-D4b 蛋白的表达和分布。
MAGE-D4mRNA 在 9 种 HCC 细胞系中的 5 种和 94 例原发性 HCC 中的 34 例中过表达（36.2%）。高表达 MAGE-D4 的患者中位总生存期（14.8 个月比 118 个月，P<0.001）和无复发生存期（2.7 个月比 18.3 个月，P<0.001）明显更短。总生存的多因素分析显示，MAGE-D4 过表达是独立的生存预后因素（危险比 2.88，P=0.009），且与高甲胎蛋白浓度（P<0.001）、肿瘤分化差（P=0.003）和血管侵犯（P=0.021）显著相关。MAGE-D4b 蛋白的表达模式与 MAGE-D4mRNA 的表达模式一致。
MAGE-D4 的过表达可能是 HCC 患者早期复发和死亡的预测标志物。
