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Overexpression of MAGE-A9 Is Predictive of Poor Prognosis in Epithelial Ovarian Cancer.

ABSTRACT: The cancer testis antigen, melanoma-associated antigen A9 (MAGE-A9), is expressed in many kinds of different human cancers, and is an important target for immunotherapy. However, the clinicopathologic significance of MAGE-A9 in epithelial ovarian cancer (EOC) is unknown. In this study, real-time PCR (12 carcinomas of high FIGO stage, 12 carcinomas of low FIGO stage, and 20 normal ovary or fallopian tube tissues) and immunohistochemistry by tissue microarrays (128 carcinomas and 112 normal ovary or fallopian tube tissues, benign or borderline ovarian tumor tissues) were performed to characterize expression of MAGE-A9 in EOC. We found that significantly higher MAGE-A9 mRNA expression in EOC tumors than that in normal ovary or fallopian tube tissues (all P < 0.05). Protein expression of MAGE-A9 was significantly associated with FIGO stage, high histological grade, level of CA-125 and metastasis. Consistent with the associated poor clinicopathologic features, patients with MAGE-A9(H (high-expressing)) tumors had a worse overall survival as compared to patients with MAGE-A9(L (low or none-expressing)) tumors. Further studies revealed that MAGE-A9 overexpression was an independent prognostic factor for overall survival (OS). Multivariate analysis showed that patients with MAGE-A9 overexpressing tumors had extremely poor OS. These findings indicate that MAGE-A9 expression may be helpful in predicting EOC prognosis.

SUBMITTER: Xu Y

PROVIDER: S-EPMC4502509 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:BackgroundAcetyl-CoA acetyltransferase 2 (ACAT2) is a lipid metabolism enzyme and rarely was researched in epithelial ovarian cancer (EOC).MethodsACAT2 expressions were confirmed in two pairs of cell lines (A2780 and A2780/DDP, OVCAR8 and OVCAR8/DDP) from Gene Expression Omnibus database by bioinformatics analysis, and in A2780 and A2780/DDP cell lines by quantitative real-time polymerase chain reaction and western blotting. Tissue samples were stained by immunohistochemistry and scored for ACAT2 expression. The relationships between ACAT2 expression and clinicopathological characteristics were analyzed by χ2 test. The prognosis of ACAT2 was analyzed by the log-rank tests and Cox regression models.ResultsACAT2 was remarkably upregulated in the above drug-resistant cell lines by mRNA (all P < 0.05) and protein expression (P = 0.026) than those in sensitive ones. Patients were classified as ACAT2-high (n = 51) and ACAT2-low (n = 26) according to immunohistochemical score. ACAT2 expression had a significantly inverse correlation with FIGO stage (P = 0.030) and chemo-response (P = 0.041). A marginal statistical significance existed in ACAT2 expression and ascites volume (P = 0.092). Univariate analysis suggested that high-expressed ACAT2 was associated with decreased platinum-free interval (PFI) (8.57 vs. 14.13 months, P = 0.044), progression-free survival (PFS) (14.12 vs. 19.79 months, P = 0.039) and overall survival (OS) (36.89 vs. 52.40 months, P = 0.044). Multivariate analysis demonstrated that ACAT2 expression (hazard ratio = 2.18, 95% confidence interval: 1.15-4.11, P = 0.017) affected OS independently, rather than PFI and PFS.ConclusionThe expression of ACAT2 in A2780/DDP and OVCAR8/DDP was higher than the corresponding A2780 and OVCAR8. High-expressed ACAT2 was associated with advanced FIGO stage, chemo-resistance, and decreased PFI, PFS and OS. It was an independent prognostic factor of OS in EOC.

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Overexpression of MAGE-A9 Is Predictive of Poor Prognosis in Epithelial Ovarian Cancer.

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