Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunotherapy.

Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunotherapy.
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DOI:
10.1186/1479-5876-4-27
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发表时间:
2006-07-04
影响因子:
7.4
通讯作者:
Gillis JS
Gillis JS
中科院分区:
医学2区
文献类型:
--
作者:
Gillis JS

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近年来,在开发癌症疫苗治疗方面取得了令人鼓舞的进展,特别是黑色素瘤。然而,具有临床意义的结果的总体发生率仍然很低。本研究使用先前研究的微阵列数据集来检查癌细胞系中的基因表达模式,目的是更好地了解肿瘤微环境。采用Promax旋转变换对来自3个微阵列数据集的90个癌细胞系进行主成分分析,这些数据集已在互联网上作为先前出版物的补充信息提供。在每个分析中,鉴定了一种明确定义的黑素瘤组分,其含有编码酶(即氨酰环化酶)的基因,所述酶与来自各种明确确立的黑素瘤生物标志物(如法师-3和MART-1)的基因一样高度表达,所述生物标志物经常用于黑素瘤疫苗的临床试验。由于谷氨酰胺环化酶将谷氨酰胺和谷氨酸转化为焦谷氨酸形式,因此它可能干扰使用在其N-末端具有谷氨酰胺或谷氨酸的肽的疫苗的肿瘤破坏过程。找到抑制肿瘤微环境中的氨酰环化酶活性的方法可能有助于提高某些黑色素瘤疫苗的有效性。
In recent years encouraging progress has been made in developing vaccine treatments for cancer, particularly with melanoma. However, the overall rate of clinically significant results has remained low. The present research used microarray datasets from previous investigations to examine gene expression patterns in cancer cell lines with the goal of better understanding the tumor microenvironment. Principal Components Analyses with Promax rotational transformations were carried out with 90 cancer cell lines from 3 microarray datasets, which had been made available on the internet as supplementary information from prior publications. In each of the analyses a well defined melanoma component was identified that contained a gene coding for the enzyme, glutaminyl cyclase, which was as highly expressed as genes from a variety of well established biomarkers for melanoma, such as MAGE-3 and MART-1, which have frequently been used in clinical trials of melanoma vaccines. Since glutaminyl cyclase converts glutamine and glutamic acid into a pyroglutamic form, it may interfere with the tumor destructive process of vaccines using peptides having glutamine or glutamic acid at their N-terminals. Finding ways of inhibiting the activity of glutaminyl cyclase in the tumor microenvironment may help to increase the effectiveness of some melanoma vaccines.
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