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鉴定 MAGEA12 为胃癌的预后外显基因。

Identification of MAGEA12 as a prognostic outlier gene in gastric cancers.

出版信息

Neoplasma. 2017;64(2):238-243. doi: 10.4149/neo_2017_210.

DOI:10.4149/neo_2017_210
PMID:28043151
Abstract

Melanoma antigen (MAGE) family genes are frequently over-expressed in a subset population of multiple cancers, and serve as idea therapeutic targets; however, their distribution pattern in gastric cancers has not yet been evaluated. In this study, we first performed a cancer outlier profile analysis (COPA) on a series of public gene expression datasets of gastric cancer, and identified MAGEA12 showing a significant outlier expression model reproducibly. We further in silico validated that MAGEA12 outlier over-expression were associated with poor clinical outcome using six microarray datasets from GEO database. We then experimentally detected the MAGEA12 expression in an independent cohort of gastric cancer samples by immunohistochemistry, and showed that over-expression of MAGEA12 in a subset of cancers was associated with later stage and reduced survival; furthermore, MAGEA12 was an independent prognostic factor in an outlier manner. Our results indicate that MAGEA12 is a novel prognostic outlier gene in gastric cancers and patterns of MAGE expression may inform individualized targeted immunotherapies.

摘要

黑色素瘤相关抗原(MAGE)家族基因在多种癌症的亚群中经常过度表达,可作为理想的治疗靶点;然而,其在胃癌中的分布模式尚未得到评估。在这项研究中,我们首先对一系列公开的胃癌基因表达数据集进行了癌症离群值特征分析(COPA),并发现 MAGEA12 表现出显著的离群表达模式,且可重复性良好。我们进一步通过从 GEO 数据库中获取的六个微阵列数据集进行了计算验证,结果表明 MAGEA12 离群高表达与不良临床结局相关。随后,我们通过免疫组织化学实验检测了另一组独立的胃癌样本中的 MAGEA12 表达情况,并发现癌症亚群中 MAGEA12 的过表达与晚期和生存降低有关;此外,MAGEA12 以离群的方式成为一个独立的预后因素。我们的结果表明,MAGEA12 是胃癌中一种新的预后离群基因,MAGE 的表达模式可能为个体化靶向免疫治疗提供信息。

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