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

Yunzhao Xu,Chenyi Wang,Yuquan Zhang,Lizhou Jia,Jianfei Huang

doi:10.1038/srep12104

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-A9H (high-expressing) tumors had a worse overall survival as compared to patients with MAGE-A9L (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.

Highlights

Ovarian cancer, as one of the most common cancers worldwide, is the most lethal of all gynecologic malignant tumors with no less than 204,000 new cases and 125,000 deaths each year1. 5-year survival remains below 50% and tumor recurrence is the main factor for failure of ovarian cancer therapy following surgery[2]
MAGE-A is a multigene family consisting of 12 homologous genes (MAGE-A1–MAGE-A12) located on chromosome Xq2818,19 where they code for antigens that are recognized by cytolytic T lymphocytes (CTL)
To evaluate the melanoma-associated antigen A9 (MAGE-A9) mRNA expression in epithelial ovarian cancer (EOC) patients, RNA was isolated from 12 high FIGO stage (III–IV) and 12 low FIGO stage (I–II) using real-time PCR

Summary

Introduction

As one of the most common cancers worldwide, is the most lethal of all gynecologic malignant tumors with no less than 204,000 new cases and 125,000 deaths each year1. 5-year survival remains below 50% and tumor recurrence is the main factor for failure of ovarian cancer therapy following surgery[2]. Increasing evidence suggests that a contribution of MAGE-A genes family to cancer progression and metastasis and a relationship with a poor clinical outcome[20,21]. Based on these findings, the use of MAGE-A gene-based cancer immunotherapy is under clinical demonstration in several malignancies including metastatic melanoma and non-small cell lung cancer[22,23]. We determined MAGE-A9 protein expression in ovarian epithelial tumor samples and analyzed the correlation between MAGE-A9 and other clinicopathologic features in a group of patients with EOC

Methods

Results

Conclusion