Analysis of the cancer genome atlas (TCGA) database identifies an inverse relationship between interleukin-13 receptor α1 and α2 gene expression and poor prognosis and drug resistance in subjects with glioblastoma multiforme.
Analysis of the cancer genome atlas (TCGA) database identifies an inverse relationship between interleukin-13 receptor α1 and α2 gene expression and poor prognosis and drug resistance in subjects with glioblastoma multiforme.
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DOI：
10.1007/s11060-017-2680-9
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发表时间：
2018-03
影响因子：
3.9
通讯作者：
Puri RK
中科院分区：
文献类型：
--
作者：
Han J;Puri RK
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性脑肿瘤。临床上正在测试各种靶向药物，包括癌症疫苗、免疫毒素、抗体和用于GBM的T细胞免疫疗法。我们以前曾报道过IL-13受体复合物的α1和α2亚单位在GBM中过表达。我们正在研究IL-13 R α1和α2在GBM肿瘤中表达的意义。为了阐明IL-13 R α1和α2表达与GBM受试者的严重程度和患病率之间的可能关系，我们分析了基因表达（通过微阵列）和公共癌症基因组图谱（TCGA）数据库（目前称为全球数据共享区）中的临床数据。超过40%的GBM样本IL-13 R α2 mRNA呈高阳性（Log 2 ≥ 2），而只有不到16%的样本IL-13 R α1 mRNA呈高阳性。与IL-13 R α 1和α 2 mRNA阴性肿瘤受试者相比，IL-13 R α 1和α 2 mRNA高表达肿瘤受试者的生存率显著较低，无论其接受何种治疗。我们进一步观察到IL-13 R α2基因表达与GBM对替莫唑胺（TMZ）化疗的耐药性相关。GBM中IL-13 R α2基因的表达似乎与参与IL-13 R复合物形成的其他链（IL-13 R α1或IL-4 R α）的基因表达无关。而IL-4 R α和IL-13 R α1基因表达之间呈正相关。通过RNA-Seq数据验证IL-13 R α2基因表达的芯片数据。对TCGA数据的深入分析表明，免疫抑制基因（如FMOD、CCL 2、OSM等）在IL-13 R α2阳性的肿瘤中呈高表达，而在IL-13 R α2阴性的肿瘤中不表达。这些结果表明，高水平的IL-13 R mRNA表达与患者预后不良之间存在直接相关性，与IL-13 R α2相关的免疫抑制基因可能在肿瘤进展中发挥作用。这些发现对于理解IL-13 R在GBM和潜在的其他癌症发病机制中的作用具有重要意义。 本文的在线版本（10.1007/s11060-017-2680-9）包含补充材料，可供授权用户使用。
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. A variety of targeted agents are being tested in the clinic including cancer vaccines, immunotoxins, antibodies and T cell immunotherapy for GBM. We have previously reported that IL-13 receptor subunits α1 and α2 of IL-13R complex are overexpressed in GBM. We are investigating the significance of IL-13Rα1 and α2 expression in GBM tumors. In order to elucidate a possible relationship between IL-13Rα1 and α2 expression with severity and prognoses of subjects with GBM, we analyzed gene expression (by microarray) and clinical data available at the public The Cancer Genome Atlas (TCGA) database (Currently known as Global Data Commons). More than 40% of GBM samples were highly positive for IL-13Rα2 mRNA (Log2 ≥ 2) while only less than 16% samples were highly positive for IL-13Rα1 mRNA. Subjects with high IL-13Rα1 and α2 mRNA expressing tumors were associated with a significantly lower survival rate irrespective of their treatment compared to subjects with IL-13Rα1 and α2 mRNA negative tumors. We further observed that IL-13Rα2 gene expression is associated with GBM resistance to temozolomide (TMZ) chemotherapy. The expression of IL-13Rα2 gene did not seem to correlate with the expression of genes for other chains involved in the formation of IL-13R complex (IL-13Rα1 or IL-4Rα) in GBM. However, a positive correlation was observed between IL-4Rα and IL-13Rα1 gene expression. The microarray data of IL-13Rα2 gene expression was verified by RNA-Seq data. In depth analysis of TCGA data revealed that immunosuppressive genes (such as FMOD, CCL2, OSM, etc.) were highly expressed in IL-13Rα2 positive tumors, but not in IL-13Rα2 negative tumors. These results indicate a direct correlation between high level of IL-13R mRNA expression and poor patient prognosis and that immunosuppressive genes associated with IL-13Rα2 may play a role in tumor progression. These findings have important implications in understanding the role of IL-13R in the pathogenesis of GBM and potentially other cancers. The online version of this article (10.1007/s11060-017-2680-9) contains supplementary material, which is available to authorized users.
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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：
15.9
作者：
Kitange, Gaspar J.;Carlson, Brett L.;Sarkaria, Jann N.
通讯作者：
Sarkaria, Jann N.
影响因子：
4.8
作者：
DEBINSKI, W;OBIRI, NI;PURI, RK
通讯作者：
PURI, RK
影响因子：
3.7
作者：
Brown CE;Warden CD;Starr R;Deng X;Badie B;Yuan YC;Forman SJ;Barish ME
通讯作者：
Barish ME
DOI：
10.1158/1078-0432.ccr-15-0428
发表时间：
2015-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Brown CE;Badie B;Barish ME;Weng L;Ostberg JR;Chang WC;Naranjo A;Starr R;Wagner J;Wright C;Zhai Y;Bading JR;Ressler JA;Portnow J;D'Apuzzo M;Forman SJ;Jensen MC
通讯作者：
Jensen MC