Li N, Hou R, Zhao L M, Gu G, Hou S Y
Department of Oncology, the Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.
Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050019, China.
Zhonghua Zhong Liu Za Zhi. 2021 Aug 23;43(8):821-826. doi: 10.3760/cma.j.cn112152-20200116-00043.
To analyze the expression pattern, mechanism and clinical significance of melanoma-associated antigen-C2 (MAGE-C2) in tumor-free breast specimens, breast benign disease specimens and breast cancer specimens. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to investigate the expressions of MAGE-C2 in 60 tumor-free breast specimens, 60 breast benign disease specimens and 60 breast cancer specimens. The correlation of MAGE-C2 expression with clinicopathological parameters and prognosis of breast cancer patients were analyzed. The expression of MAGE-C2 was also detected by RT-PCR in breast cancer cell MCF-7 and MDA-MB-231 treated with DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA). The positive expression rates of MAGE-C2 mRNA and protein were 61.7% (37/60) and 58.3% (35/60) in breast cancer specimens, respectively, while negative expressed in breast and begin disease specimens. MAGE-C2 protein expression was associated with tumor grade, histological type and blood vessel invasion of breast cancer patients (<0.05). The incidence of recurrence-free survival of patients with positive MAGE-C2 expression were lower than that of patients with negative MAGE-C2 expression (<0.05). Multivariate Cox regression analysis showed that the clinical stage (<0.01), lymph node metastasis (<0.05) and MAGE-C2 expression (<0.05) were the independent prognostic factors of breast cancer patients. The MAGE-C2 mRNA was not observed in the control and TSA treated breast cancer cells while upregulated in the 5-aza-CdR treated cells. Besides, 5-aza-CdR combined with TSA further enhanced MAGE-C2 mRNA level in breast cancer cells (<0.05). MAGE-C2 is one of the tumor-specific antigen and its expression is related with the poor prognosis of breast cancer patients. DNA methylation and histone acetylation may be an important regulation mechanism of MAGE-C2 gene expression.
分析黑色素瘤相关抗原C2(MAGE-C2)在乳腺良性疾病标本、癌旁乳腺组织标本及乳腺癌组织标本中的表达模式、机制及临床意义。采用逆转录聚合酶链反应(RT-PCR)和免疫组化方法检测60例癌旁乳腺组织标本、60例乳腺良性疾病标本及60例乳腺癌组织标本中MAGE-C2的表达情况。分析MAGE-C2表达与乳腺癌患者临床病理参数及预后的相关性。采用DNA甲基化酶抑制剂5-氮杂-2'-脱氧胞苷(5-aza-CdR)和组蛋白去乙酰化酶抑制剂曲古抑菌素A(TSA)处理人乳腺癌细胞MCF-7和MDA-MB-231,RT-PCR法检测MAGE-C2的表达。结果显示,乳腺癌组织标本中MAGE-C2 mRNA和蛋白的阳性表达率分别为61.7%(37/60)和58.3%(35/60),而在乳腺良性疾病及癌旁乳腺组织标本中均呈阴性表达。MAGE-C2蛋白表达与乳腺癌患者的肿瘤分级、组织学类型及血管侵犯有关(P<0.05)。MAGE-C2表达阳性患者的无复发生存率低于MAGE-C2表达阴性患者(P<0.05)。多因素Cox回归分析显示,临床分期(P<0.01)、淋巴结转移(P<0.05)及MAGE-C2表达(P<0.05)是乳腺癌患者的独立预后因素。TSA处理组细胞中未检测到MAGE-C2 mRNA表达,5-aza-CdR处理组细胞中MAGE-C2 mRNA表达上调,5-aza-CdR联合TSA处理组细胞中MAGE-C2 mRNA表达进一步升高(P<0.05)。MAGE-C2是肿瘤特异性抗原之一,其表达与乳腺癌患者预后不良有关。DNA甲基化和组蛋白乙酰化可能是MAGE-C2基因表达的重要调控机制。