Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer
Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer
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HMGA2 表达升高与癌症侵袭性相关，并预示乳腺癌的不良预后
DOI：
10.1016/j.canlet.2016.04.005
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发表时间：
2016-07-01
期刊：
影响因子：
9.7
通讯作者：
Wang, Xiaochen
中科院分区：
文献类型：
--
作者：
Wu, Jingjing;Zhang, Shizhen;Wang, Xiaochen
高迁移率族AT-钩2（HMGA 2）参与广泛的生物过程，并在几种肿瘤中上调。在这里，我们收集了273例乳腺癌（BC）标本作为训练集，310例标本作为验证集，通过免疫组织化学染色检测HMGA 2的表达。HMGA 2的表达与肿瘤的分级和生存率呈显著正相关。亚组分析显示高水平HMGA 2与预后不良相关，尤其在低病理分级和非三阴性乳腺癌亚组中。基因集富集分析（GSEA）显示HMGA 2水平与化生和间充质表型的基因表达特征之间存在显著正相关。重要的是，我们还观察到HMGA 2的异位表达促进了乳腺癌细胞的迁移和侵袭，并保护癌细胞免受刺激P53（Ser 15）磷酸化的药物的遗传毒性应激。结论：HMGA 2的表达可能提示乳腺癌的恶性程度更高。因此，我们认为HMGA 2可以作为一个预后不良的生物标志物和治疗BC肿瘤的新靶点。(C)2016爱思唯尔爱尔兰有限公司版权所有。
High mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors. Here, we collected 273 breast cancer (BC) specimens as a training set and 310 specimens as a validation set to examine the expression of HMGA2 by immunohistochemical staining. It was found that HMGA2 expression was significantly positively correlated with advanced tumor grade and poor survival. Subgroup analysis indicated that high level of HMGA2 was significantly correlated with poor prognosis, especially in the subgroups of stage low pathological grade and non triple negative breast cancer cases. Gene set enrichment analysis (GSEA) demonstrated a significant positive correlation between HMGA2 level and the gene expression signature of metaplastic and mesenchymal phenotype. Importantly, we also observed that ectopic expression of HMGA2 promoted the migration and invasion of breast cancer cells, and protected cancer cells against genotoxic stress from agents stimulating P53 (Ser15) phosphorylation. As a conclusion, expression of HMGA2 might indicate more advanced malignancy of breast cancer. Thus we believe HMGA2 could serve as a biomarker of poor prognosis and a novel target in treating BC tumors. (C) 2016 Elsevier Ireland Ltd. All rights reserved.