Xu Xin, Tang Xiaojun, Lu Meiping, Tang Qi, Zhang Huilin, Zhu Huijun, Xu Ning, Zhang Dawei, Xiong Lin, Mao Yuan, Zhu Jin
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.
Exp Mol Pathol. 2014 Dec;97(3):579-84. doi: 10.1016/j.yexmp.2014.11.001. Epub 2014 Nov 5.
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.
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。