Glioma IL13Rα2 is associated with mesenchymal signature gene expression and poor patient prognosis.
Glioma IL13Rα2 is associated with mesenchymal signature gene expression and poor patient prognosis.
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DOI：
10.1371/journal.pone.0077769
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Barish ME
中科院分区：
文献类型：
--
作者：
Brown CE;Warden CD;Starr R;Deng X;Badie B;Yuan YC;Forman SJ;Barish ME
成功的胶质瘤免疫治疗的一个主要挑战是识别和表征有效的靶点。我们采用生物信息学的方法来了解IL-13受体α2(IL13Rα2)在脑肿瘤中表达的生物学背景及其对患者生存的功能意义。查询多个基因表达数据库，我们发现IL13Rα2的表达随着胶质瘤恶性程度的升高而增加，高级别肿瘤的表达呈双峰型，约58%的世界卫生组织IV级胶质瘤过度表达该受体。从几个方面来看，IL13Rα2在患者样本和低传代原发胶质瘤系中的表达与定义间充质亚类肿瘤的特征基因的表达最一致，而与两项研究定义的神经特征基因负相关。增殖性标志性基因也发现了正相关性，而与经典或神经标志性基因没有发现一致的相关性。通过IPA分析探讨这种间充质联系的潜在功能后果表明，IL13Rα2的表达与间叶细胞亚类肿瘤特有的促炎和免疫通路的激活有关。此外，生存分析表明，IL13Rα2的过度表达与患者预后不良有关，单基因相关性将IL13Rα2排在与WHO IV型胶质瘤生存相关的总基因表达探针的前~1%。这项研究更好地定义了IL13Rα2表达与间充质签名基因表达和患者预后不良之间的关系。因此，它强调了IL13Rα2作为治疗靶点的效用，并有助于在目前和未来的临床试验中确定最有可能对免疫治疗产生反应的患者群体。
A major challenge for successful immunotherapy against glioma is the identification and characterization of validated targets. We have taken a bioinformatics approach towards understanding the biological context of IL-13 receptor α2 (IL13Rα2) expression in brain tumors, and its functional significance for patient survival. Querying multiple gene expression databases, we show that IL13Rα2 expression increases with glioma malignancy grade, and expression for high-grade tumors is bimodal, with approximately 58% of WHO grade IV gliomas over-expressing this receptor. By several measures, IL13Rα2 expression in patient samples and low-passage primary glioma lines most consistently correlates with the expression of signature genes defining mesenchymal subclass tumors and negatively correlates with proneural signature genes as defined by two studies. Positive associations were also noted with proliferative signature genes, whereas no consistent associations were found with either classical or neural signature genes. Probing the potential functional consequences of this mesenchymal association through IPA analysis suggests that IL13Rα2 expression is associated with activation of proinflammatory and immune pathways characteristic of mesenchymal subclass tumors. In addition, survival analyses indicate that IL13Rα2 over-expression is associated with poor patient prognosis, a single gene correlation ranking IL13Rα2 in the top ~1% of total gene expression probes with regard to survival association with WHO IV gliomas. This study better defines the functional consequences of IL13Rα2 expression by demonstrating association with mesenchymal signature gene expression and poor patient prognosis. It thus highlights the utility of IL13Rα2 as a therapeutic target, and helps define patient populations most likely to respond to immunotherapy in present and future clinical trials.
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影响因子：
11.2
作者：
Brown CE;Starr R;Martinez C;Aguilar B;D'Apuzzo M;Todorov I;Shih CC;Badie B;Hudecek M;Riddell SR;Jensen MC
通讯作者：
Jensen MC
影响因子：
5.7
作者：
Hsi LC;Kundu S;Palomo J;Xu B;Ficco R;Vogelbaum MA;Cathcart MK
通讯作者：
Cathcart MK
影响因子：
11.2
作者：
Jarboe, John S.;Johnson, Kory R.;Park, John K.
通讯作者：
Park, John K.
影响因子：
6.2
作者：
Kawakami, M;Kawakami, K;Puri, RK
通讯作者：
Puri, RK
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y