Improving Seroreactivity-Based Detection of Glioma
Improving Seroreactivity-Based Detection of Glioma
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DOI：
10.1593/neo.91018
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发表时间：
2009-12-01
期刊：
影响因子：
4.8
通讯作者：
Meese, Eckart
中科院分区：
文献类型：
--
作者：
Ludwig, Nicole;Keller, Andreas;Meese, Eckart
血清反应性分析成为微创癌症检测的有价值的技术。最近，我们提供了使用有限数量的免疫原性抗原进行胶质瘤血清分析的适用性的第一个证据。在这里，我们筛选了57个胶质瘤和60个健康血清的自身抗体对1827大肠杆菌表达的克隆，包括509框内肽序列。通过线性支持向量机方法，我们计算了100个重复分类的平均特异性，灵敏度和准确性。对胶质瘤患者血清和正常人血清的鉴别诊断特异性为90.28%，敏感性为87.31%，准确性为88.84%。我们还能够区分世界卫生组织IV级胶质瘤血清与健康血清，特异性为98.45%，敏感性为80.93%，准确性为92.88%。为了根据抗原的信息含量对其进行排序，我们计算了每个克隆的受试者操作特征曲线值下的面积。总之，我们发现了46个免疫原性克隆，包括16个框内克隆，这些克隆为胶质瘤血清与健康血清的分类提供了信息。对于胶质母细胞瘤与健康血清的分离，我们发现了91个信息克隆，包括26个框内克隆。用于神经胶质瘤血清与健康血清的分类的最适合的框内克隆对应于先前与神经胶质瘤相关的波形蛋白基因（Vim）。在未来，胶质瘤自身抗体标记不仅可能被证明是有用的诊断，但也提供了前景的个性化免疫治疗。
Seroreactivity profiling emerges as valuable technique for minimal invasive cancer detection. Recently, we provided first evidence for the applicability of serum profiling of glioma using a limited number of immunogenic antigens. Here, we screened 57 glioma and 60 healthy sera for autoantibodies against 1827 Escherichia coli expressed clones, including 509 in-frame peptide sequences. By a linear support vector machine approach, we calculated mean specificity, sensitivity, and accuracy of 100 repetitive classifications. We were able to differentiate glioma sera from sera of the healthy controls with a specificity of 90.28%, a sensitivity of 87.31% and an accuracy of 88.84%. We were also able to differentiate World Health Organization grade IV glioma sera from healthy sera with a specificity of 98.45%, a sensitivity of 80.93%, and an accuracy of 92.88%. To rank the antigens according to their information content, we computed the area under the receiver operator characteristic curve value for each clone. Altogether, we found 46 immunogenic clones including 16 in-frame clones that were informative for the classification of glioma sera versus healthy sera. For the separation of glioblastoma versus healthy sera, we found 91 informative clones including 26 in-frame clones. The best-suited in-frame clone for the classification glioma sera versus healthy sera corresponded to the vimentin gene (VIM) that was previously associated with glioma. In the future, autoantibody signatures in glioma not only may prove useful for diagnosis but also offer the prospect for a personalized immune-based therapy.