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连接卵巢癌转录组和免疫组。

Linking the ovarian cancer transcriptome and immunome.

作者信息

Rapberger Ronald, Perco Paul, Sax Cornelia, Pangerl Thomas, Siehs Christian, Pils Dietmar, Bernthaler Andreas, Lukas Arno, Mayer Bernd, Krainer Michael

机构信息

Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, A-1090 Vienna, Austria.

出版信息

BMC Syst Biol. 2008 Jan 3;2:2. doi: 10.1186/1752-0509-2-2.

Abstract

BACKGROUND

Autoantigens have been reported in a variety of tumors, providing insight into the interplay between malignancies and the immune response, and also giving rise to novel diagnostic and therapeutic concepts. Why certain tumor-associated proteins induce an immune response remains largely elusive.

RESULTS

This paper analyzes the proposed link between increased abundance of a protein in cancerous tissue and the increased potential of the protein for induction of a humoral immune response, using ovarian cancer as an example. Public domain data sources on differential gene expression and on autoantigens associated with this malignancy were extracted and compared, using bioinformatics analysis, on the levels of individual genes and proteins, transcriptional coregulation, joint functional pathways, and shared protein-protein interaction networks. Finally, a selected list of ovarian cancer-associated, differentially regulated proteins was tested experimentally for reactivity with antibodies prevalent in sera of ovarian cancer patients.Genes reported as showing differential expression in ovarian cancer exhibited only minor overlap with the public domain list of ovarian cancer autoantigens. However, experimental screening for antibodies directed against antigenic determinants from ovarian cancer-associated proteins yielded clear reactions with sera.

CONCLUSION

A link between tumor protein abundance and the likelihood of induction of a humoral immune response in ovarian cancer appears evident.

摘要

背景

多种肿瘤中已报道存在自身抗原,这为深入了解恶性肿瘤与免疫反应之间的相互作用提供了线索,同时也催生了新的诊断和治疗理念。为何某些肿瘤相关蛋白会引发免疫反应,目前仍不清楚。

结果

本文以卵巢癌为例,分析了癌组织中某种蛋白丰度增加与该蛋白诱导体液免疫反应的潜力增加之间的潜在联系。利用生物信息学分析,从个体基因和蛋白质水平、转录共调控、联合功能途径以及共享的蛋白质-蛋白质相互作用网络等方面,提取并比较了有关差异基因表达和与这种恶性肿瘤相关的自身抗原的公共领域数据源。最后,对选定的与卵巢癌相关的差异调节蛋白列表进行实验测试,以检测其与卵巢癌患者血清中普遍存在的抗体的反应性。报道显示在卵巢癌中存在差异表达的基因与卵巢癌自身抗原的公共领域列表仅有少量重叠。然而,针对来自卵巢癌相关蛋白的抗原决定簇的抗体进行实验筛选时,血清出现了明显反应。

结论

在卵巢癌中,肿瘤蛋白丰度与诱导体液免疫反应的可能性之间的联系似乎很明显。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f3/2265674/ab22e5f1ebff/1752-0509-2-2-1.jpg

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