Melanoma-associated antigen-A1 expression predicts resistance to docetaxel and paclitaxel in advanced and recurrent gastric cancer.
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.
Suzuki
Takahisa
T
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8551, Japan.
Yoshida
Kazuhiro
K
Wada
Yoshiyuki
Y
Hamai
Yoichi
Y
Sentani
Kazuhiro
K
Oue
Naohide
N
Yasui
Wataru
W
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D017239:Paclitaxel / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use*; D014162:Transfection
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel