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MAGE-A9的过表达预示着乳腺癌的不良预后。

Overexpression of MAGE-A9 predicts unfavorable outcome in breast cancer.

作者信息

Xu Xin, Tang Xiaojun, Lu Meiping, Tang Qi, Zhang Huilin, Zhu Huijun, Xu Ning, Zhang Dawei, Xiong Lin, Mao Yuan, Zhu Jin

机构信息

The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center, Nanjing Medical University, No. 140 Hanzhong Road, Nanjing 210029, China; The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, No. 140 Hanzhong Road, Nanjing 210029, China.

Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210011, China.

出版信息

Exp Mol Pathol. 2014 Dec;97(3):579-84. doi: 10.1016/j.yexmp.2014.11.001. Epub 2014 Nov 5.

Abstract

Melanoma-associated antigens (MAGEs) are a group of well-characterized members of the cancer/testis antigen (CTA) family, which is one of the largest groups of human tumor-associated antigens. MAGE-A9 is a particular member in the context of the MAGE-A gene family and was defined as presenting prognostic relevance in certain type of human cancer. However, the expression of MAGE-A9 in invasive ductal breast cancer (IDC) and the relationship with the clinical attributes of IDC, especially prognostic characteristic, remain poorly understood. In this present study, one-step quantitative reverse transcription polymerase chain reaction (18 fresh-frozen IDC tissues and corresponding non-cancerous tissues) and immunohistochemistry by tissue microarrays (82 IDC tissue samples and 70 matched tumor-adjacent non-cancerous tissue samples) were performed to characterize expression of the MAGE-A9 gene in IDC. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of IDC. The results of qPCR and IHC analysis showed that the expression of MAGE-A9 in IDC was significantly higher than that in corresponding non-cancerous tissue. Moreover, the expression level of MAGE-A9 protein in IDC was significantly related to histological grade (p = 0.011) and distant metastasis (p = 0.019). Multivariate analysis with the Cox regression model showed that MAGE-A9 protein expression (p = 0.009), histological grade (p = 0.014), lymph node metastasis (p = 0.012) and distant metastasis (p = 0.011) were independent prognostic factors for overall survival of IDC patients. The data suggest that MAGE-A9 expression is correlated with malignant attributes of IDC and it may serve as a novel prognostic factor and an ideal candidate for targeted therapy in IDC treatment.

摘要

黑色素瘤相关抗原(MAGEs)是癌症/睾丸抗原(CTA)家族中一组特征明确的成员,CTA家族是人类肿瘤相关抗原中最大的群体之一。MAGE-A9是MAGE-A基因家族中的一个特殊成员,在某些类型的人类癌症中被确定具有预后相关性。然而,MAGE-A9在浸润性导管癌(IDC)中的表达及其与IDC临床特征(尤其是预后特征)的关系仍知之甚少。在本研究中,采用一步定量逆转录聚合酶链反应(18个新鲜冷冻的IDC组织及相应的癌旁组织)和组织芯片免疫组化(82个IDC组织样本和70个配对的肿瘤旁癌旁组织样本)来检测MAGE-A9基因在IDC中的表达。进行Kaplan-Meier生存分析和Cox回归分析以评估IDC的预后。qPCR和IHC分析结果显示,MAGE-A9在IDC中的表达显著高于相应的癌旁组织。此外,MAGE-A9蛋白在IDC中的表达水平与组织学分级(p = 0.011)和远处转移(p = 0.019)显著相关。Cox回归模型多因素分析显示,MAGE-A9蛋白表达(p = 0.009)、组织学分级(p = 0.014)、淋巴结转移(p = 0.012)和远处转移(p = 0.011)是IDC患者总生存的独立预后因素。数据表明,MAGE-A9表达与IDC的恶性特征相关,它可能作为一种新的预后因素及IDC治疗中靶向治疗的理想候选靶点。

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