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基于 DNA 微阵列的 MAGE-A11 在食管鳞癌中的预后意义及相关基因的鉴定。

Prognostic Significance of MAGE-A11 in Esophageal Squamous Cell Carcinoma and Identification of Related Genes Based on DNA Microarray.

机构信息

Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China; Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

出版信息

Arch Med Res. 2016 Apr;47(3):151-61. doi: 10.1016/j.arcmed.2016.06.001. Epub 2016 Jun 27.

Abstract

BACKGROUND AND AIMS

This study aims to investigate the expression pattern of melanoma-associated antigen-A11 (MAGE-A11) in esophageal squamous cell carcinoma (ESCC) specimens and analyze its prognostic significance for ESCC patients. In addition, the purpose of our study was also to explore the biological function of MAGE-A11 in ESCC cells based on DNA microarray.

METHODS

Immunohistochemistry was used to detect the expression of MAGE-A11 in ESCC specimens, and its prognostic significance was analyzed by statistical analysis. DNA microarray and quantitative RT-PCR were used to explore the different expression of MAGE-A11 downstream genes in ESCC cells. Cell invasion assay and MTT assay were used to detect the effect of MAGE-A11 cDNA on the invasion and proliferation of ESCC cells.

RESULTS

Of the ESCC specimens, 59.3% showed positive MAGE-A11 expression. MAGE-A11 expression in ESCC specimens was positively associated with distant lymph node metastasis. Overall survival of ESCC patients with positive MAGE-A11 expression was shorter than in patients with negative MAGE-A11 expression. Multivariate Cox regression analysis showed MAGE-A11 expression is an independent poor prognostic factor for ESCC patients. Overexpression of MAGE-A11 changed a variety of gene expressions, which was associated with various cell functions such as protein ubiquitination, cell proliferation and apoptosis, tumor invasion and metastasis. Overexpression of MAGE-A11 directly increased the invasion and proliferation of ESCC cells.

CONCLUSIONS

MAGE-A11 is an independent poor prognostic marker for ESCC patients. MAGE-A11 regulates various cell functions and directly increases the invasion and proliferation of ESCC cells.

摘要

背景与目的

本研究旨在探讨黑色素瘤相关抗原-A11(MAGE-A11)在食管鳞状细胞癌(ESCC)标本中的表达模式,并分析其对 ESCC 患者的预后意义。此外,我们的研究目的还在于基于 DNA 微阵列探讨 MAGE-A11 在 ESCC 细胞中的生物学功能。

方法

采用免疫组织化学法检测 ESCC 标本中 MAGE-A11 的表达,并进行统计学分析其预后意义。采用 DNA 微阵列和定量 RT-PCR 技术探讨 MAGE-A11 在 ESCC 细胞中下游基因的不同表达。采用细胞侵袭实验和 MTT 实验检测 MAGE-A11 cDNA 对 ESCC 细胞侵袭和增殖的影响。

结果

在 ESCC 标本中,59.3%显示 MAGE-A11 表达阳性。ESCC 标本中 MAGE-A11 的表达与远处淋巴结转移呈正相关。MAGE-A11 表达阳性的 ESCC 患者的总生存期短于 MAGE-A11 表达阴性的患者。多因素 Cox 回归分析表明,MAGE-A11 表达是 ESCC 患者的独立预后不良因素。MAGE-A11 的过表达改变了多种基因的表达,与各种细胞功能有关,如蛋白泛素化、细胞增殖和凋亡、肿瘤侵袭和转移。MAGE-A11 的过表达直接增加了 ESCC 细胞的侵袭和增殖。

结论

MAGE-A11 是 ESCC 患者的独立预后不良标志物。MAGE-A11 调节各种细胞功能,并直接增加 ESCC 细胞的侵袭和增殖。

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