Melanoma-associated antigen-A1 expression predicts resistance to docetaxel and paclitaxel in advanced and recurrent gastric cancer.
Melanoma-associated antigen-A1 expression predicts resistance to docetaxel and paclitaxel in advanced and recurrent gastric cancer.
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DOI：
10.3892/or.18.2.329
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发表时间：
2007-08
期刊：
影响因子：
4.2
通讯作者：
Takahisa Suzuki;Kazuhiro Yoshida;Y. Wada;Y. Hamai;K. Sentani;N. Oue;W. Yasui
中科院分区：
文献类型：
--
作者：
Takahisa Suzuki;Kazuhiro Yoshida;Y. Wada;Y. Hamai;K. Sentani;N. Oue;W. Yasui
黑色素瘤相关抗原(MAGE)基因是癌症-睾丸抗原基因，在几种人类癌症中充当免疫治疗靶点。先前的研究表明，MAGE基因的强制表达会诱导紫杉醇耐药表型。在这项研究中，我们研究了MAGE-A1的表达是否可以预测进展期和复发性胃癌(GC)对紫杉醇(多西紫杉醇或紫杉醇)化疗的反应。采用免疫组织化学方法检测41例原发胃癌组织中MAGE-A1的表达。用甲基化特异性聚合酶链式反应检测DNA去甲基化，用四甲基偶氮唑盐比色法检测MAGE-A1强制表达对紫杉类药物耐药性的影响。41例胃癌中有4例(9.8%)表达MAGE-A1。4例MAGE-A1阳性的胃癌患者均为进展性疾病，而23例部分缓解的患者均未检测到MAGE-A1的表达(P=0.0302)。MAGE-A1基因去甲基化与化疗疗效无关(P=0.7245)。MAGE-A1在TMK-1GC细胞中的强制表达增加了对紫杉醇和多西紫杉醇的敏感性。这些结果表明，虽然MAGE-A1不直接参与胃癌的耐药表型，但MAGE-A1的表达可作为预测胃癌患者对紫杉类药物耐药的指标。
Melanoma-associated antigen (MAGE) genes are cancer-testis antigen genes that serve as immunotherapy targets in several human cancers. Previous studies have revealed that the forced expression of MAGE genes induces a paclitaxel-resistant phenotype. In the present study, we examined whether the expression of MAGE-A1 could predict the response of advanced and recurrent gastric cancers (GCs) to taxan (doce-taxel or paclitaxel)-based chemotherapy. The expression of MAGE-A1 was analyzed by immunostaining in 41 primary GC samples. DNA demethylation was assessed by methylation-specific polymerase chain reaction and the effect of the forced expression of MAGE-A1 on drug resistance to taxan drugs was monitored by MTT assay. The expression of MAGE-A1 in primary GC was observed in 4 (9.8%) of 41 cases. All 4 patients with MAGE-A1-positive GC showed progressive disease, whereas MAGE-A1 expression was not detected in any of the 23 patients showing partial response (P=0.0302). There was no association between MAGE-A1 gene demethylation and response to chemotherapy (P=0.7245). The forced MAGE-A1 expression in the TMK-1 GC cell line increased the sensitivity to paclitaxel and docetaxel. These results suggest that although MAGE-A1 does not participate directly in the drug-resistant phenotype, the expression of MAGE-A1 could be a marker for the prediction of resistance to taxan-based chemotherapies in patients with GC.